I

ntr
oduct
ion

Overt hepast2 decades,cor onav i

r uses( CoVs)
have been associ ated wi th si gnificantdi sease
outbreaksi nEastAsi aandt heMi ddl eEast .The
severeacut er espiratorysyndr ome( SARS)andt he
MiddleEastr espi ratorysy ndr ome( MERS)began
toemer gei n2002and2012, respect ively.Recent l
y,
a nov elcor onav i
rus,sev er e acut er espi rat ory
syndrome cor onav irus 2 ( SARS- CoV- 2),causi ng
coronav i
rusdi sease2019( COVI D-19) ,emer gedi n
l
ate2019,andi thasposedagl obalheal t
ht hr eat ,
causi
nganongoi ngpandemi ci nmanycount r
iesand
ter
rit
or i
es( l)
.
Health wor kers wor ldwi de ar e cur rent l
y
maki ng eff orts
tocont rolfurtherdiseaseout breakscausedbyt he
nov elCoV( originallynamed2019- nCoV) ,whi ch
was f irst i dent i
fied in Wuhan Ci ty,Hubei
Prov i
nce,Chi na,on12 December2019.On11
Febr uary2020,t heWor ldHeal thOr ganizat i
on
(WHO)announcedt heof ficialdesi gnationf or
the cur rent CoV- associat ed di sease t o be
COVI D- 19,causedbySARS- CoV-2.Thepr imar y
cl
usterofpat i
entswasfoundtobeconnect ed
wit
ht heHuananSouthChinaSeafoodMar ketin
Wuhan (2)
. CoVs
bel
ongtothefamil
yCor
onavi
ri
dae(
subf amil
y
Coronavi
rinae)
,t
hemembersof
whichinfect
abroad
etatk(-
toJ.l
l
cccii
i
ly,
suti
cit
ualUni
a12sesclf
licS
proteins ofCOVI D-19 hav erevealed 27 ami no
acid subst it
uti
ons wi t
hin a l ,
273-alTiif
1O-äCid
stretch(l .Si
6) xsubsti
tuti
onsarelocatedintheRBD
(ami noacids357t o525) ,
whilefoursubst itut
ions
arei ntheRBM att heCTDoft heSl doi nain(l6)
.
Ofnot e,noami noaci dchangei sseeni nt he
RBM,whi ch bi nds di rectlyt ot he angi otensin-
conv erti
ngenzy me- 2( ACE2)r ecept ori nSARS-
CoV( 16,46) .Atpr esent ,t hemai nemphasi si s
knowi nghowmanydi ffer
enceswoul dber equired
to change t he host t ropism. Sequence
compar i
son r ev ealed l 7 nonsy nony mous
changesbet weent heear l
ysequenceofSARS-
CoV- 2andt hel ateri solatesofSARS- CoV.The
changeswer ef oundscat teredov ert hegenome
oft hev i
rus,wi thni nesubst it
utionsi nORF1ab,
ORFS ( 4 subst i
tuti
ons) ,t he spi ke gene ( 3
subst i
tuti
ons) ,and ORF7a ( si
nglesubst i
tuti
on)
(4).Not ably ,thesamenonsy nony mouschanges
wer ef oundi naf ami l
ialclust er,i
ndicatingt hatthe
viralev olutionhappeneddur ingper soD- to-person
transmi ssion (4, 47) . Such
adapt i
vcev olutioncv entsar efréquentandconst it
ute
a const ant ly ongoi ng pr ocess once t he v ir
us
spr eadsai nongnewhost s( 47).Ev ent houghno
f
unctionalchangesoccurinthcvi
rusassoci
ated
wi
th
t
hisadopti
veevol
uti
on,
closemoni
tor
ingof
thev
iral
xi
l
”ti
l
cil
cc o1 ci
›i
‘
ol1i
i
xi1”
ti
scs duc t
o cl
l
ii
ll
gcs l
i
t
l
norpliol
ogyandtr
opisi
Ti(
54) .TheEprotelnconsi
sts
ofthreedomains,namely,ashor thydrophil
lCIi
lTll
fl
O
tenvl
inal,a large hydr ophobi ct r
ansl l
iel
nbrane
domai n, and an ef f
icient C- t
ermi nal dOlTlaln
(51)TheSARS-
. CoV- 2Epr oteinrevealsaSl milar
aminoacidconsti
tutl
Ori
without any
subst i
tuti
on(16).

NPr
otei
n
TheN pr otei
nofcOr onavlrusi si vlul
tl
pur pose.
Amongsev er alfURCt l
ORs,i tpl
ay sar olelncoi nplex
format ion wi tht he v ir
algenome,f aci l
i
tates M
proteini nter act l
onneededdur ingv l
rlonassei nbly,
and enhances t he t r
anscr l
pti
on ef ficlencyoft he
vlus(
r 55,5f ›).ltcont ainst hr
eehi ghlyconser ved
and di stinctdomai ns,nal nel
y,anNTD,anRNA-
binding dOl nain ora l l
nkerr egion ( LKR) ,and a
CTD( 57) TheNTDbi
. ndswi tht he3'endof thev iral
genome.per haps v ia electr
ost atici nteract i
ons,
and i s hi ghl y diverged bot h l n l ength and
sequence ( 5S) .The char ged LKRi s ser i
ne and
arglnl
ner ichandl Sal soknownast heSR( serine
and ar gi
nine) domai n (
59) .
TheLKRi scapabl eofdirecti
nteractionwi thii
ii
'i
ti‹›
RNAl nteract ionandi sr esponslblef orcel lsignaling
(ù0,bl)
.l tal somodul atest heant i
v i
ralr esponseof
t
hehost
bywor
kingasanant
agoni
stf
ori
nter
fer
on
 Besi dest hei mpoi tantst ructuralpr oteins,the
SARS- CoV-
2genoi v‹econt alns15nsps, nspl t
onsp10andnsp12t
onsp16, and8accessor y proteins( 3a,3b, p6,7a, 7b,
öb,9b,and ORF14)( 1f›).Al lt hèseproteinsplay
aspeci fi
cr oleinv i
ral
r eplication ( 27).Unl lke the
accessor y pr oteins of SARS- CoV,SARS- CoV-2
doesnotcont ain8apr oteinandhasal onger8b
and shoHer3b pr ot ein( 16).Thensp7,nsp13,
envelope, mat rl
x, and p6 and 8b accessor y
protei
nshav enot beendet ect edwithany ai
aalROaci d
substltutionscompar edt ot hesequencesofot her
coronav iruses( lù) .
Tlie•virusstructureof SARS- CoV- 2isdepictedin
Fi
g.2.

Spikeglycoprotei
n(S)
(r
equiredfortheentr
yofthe
i
nfectiousv i
ri
onpar t
icl
e)
Membraneprot
ein(M)
(
mostabundantvi
ralpr
otei
n) Maj
orst
ruct
ural
prot
eins

Envel
opegl ycopr
otei
n(E)
(smal
lestamongthemajor
str
ucturalprotei
ns)

Nucl
eocapsi
dpr
otei
nIN)
+singl
e-st
randedposi
ti
ve
senseRNAgenome

Li
pidbi
l
ayer
FI
G2SARS-
CoV-
2vi
russt
ruct
ure.
 Init
iall
y,t he cpi cciaicr o1 t he SAI LS-CoV-2
pandemi cwasChi na,whi chr eportedasi gnifi
cant
numberofdeat hsassoci at edwi thCOVI D- 19,with
84,458labor atory -
conf inedcasesand4, 644deat hs
asof13May 2020( Fig.4).Asof 13May 2020,
SARS- CoV- 2conf irmedcaseshav ebeenr eported
i
n mor ethan210count riesapar t
fromChi na(Fi
g.3
and4)( WHOSi mat i
onRepor t114) (25,
64) .COVI D-
19hasbeenr epor tedon al lcont i
nent s except
Antarctica.For many weeks, I t
al y was
thefocusof concer nsregardi ngt helargenumber of
cases,wi t
h221, 216casesand30, 911deaths, but
now,t heUni tedSt atesi st hecount r
ywi tht he
l
argest
number ofcases, 1,322,054, and79, 634deat hs.Now,
the Uni t
ed Ki ngdom has ev en mor e cases
(226,4671)and deat hs ( 32, 692)t han I t
aly.A
John Hopki ns Uni versity web pl atform has
provideddai lyupdat esont hebasi cepi demi ology
oftheCOVI D-19out break
shi
p, named Di ‹
imoii‹l
Pri
meess, quai aii
ti
iicdin
Japanesewater
s( PortofYokohama) ,aswel las
onothercr
uiseshi
psar oundt heworld(239)( Fig.
3).The si
gnifi
cantev ent
s oft he SARS- CoV-
2/COVID- 19 vir
us out break occurr
ing si nce
8December2019ar epresentedasatimelineinFig.
5.

Me}
oresenuof
‹uwent
eronav
irusCOVt
D-19I
seeceout
break

FI
G 5Ti meli
nedepi ct
ingt
hesignifi
cantevent
st hat
occurred during the SARS-CoV-2/
COVI D-
19 virus
outbreak.Theti
meli
nedescri
best hesigni
fi
cant
events
during the curr
entSARS-CoV-2 outbreak,fr
om 8
December2019t o13May2020.

Att
hebeginning,
Chinaexperi
encedthemajor
it
y oft
he burden associated with COVID-
19 in
t
heform ofdi sease mor bi
dit
y and mor t
ali
ty
(
65) , but over timetheCOVID-
19menacemov
edt
oEur
ope,
Spi e
St
atel!
' y
tha:
..
h:, ll.
e df
nfi
rmednosd
significant l
yhigher t
hantheinitial
WHOest i
mat eof
1. 4to2. 5( 77) .Iti
stooear l
y toobt aintheexact Rd
val ue,si ncet herei sapossi bi li
tyofbi asduet o
i
nsuf ficient dat a.
Thehi gherRq val ue i si ndicati
veof
the mor e si gni f
icantpot entialofSARS- CoV- 2
transmi ssioni nasuscept i
bl epopul ation. Thisisnot
thef irstt i
mewher ethecul inar y pr act i
cesof China
hav ebeenbl amedf ortheoriginof nov elcor onav i
rus
i
nf ect ioni nhumans. Previousl y,
theani mal spresent
i
nt hel ive- ani mal mar ket wer eident ifiedt obethe
i
nt ermedi at ehost soft heSARSout breaki nChi na
(7S) .Sev er alwi l
dli
fespeci eswer efoundt oharbor
pot ent iallyev olvi
ngcor onav i
russt rainst hatcan
ov ercomet hespeci esbar rier (
79) .Oneof themai n
pr i
nci pl esofChi nesef oodcul turei st hatl ive-
slaught er ed animal s ar econsi dered
mor enut r
itious( 5).
Af ter4mont hsofst ruggl et hatl ast edf rom
December2019t oMar ch2020,t heCOVI D-19
situat ionnowseemsunder cont rol i
nChi na. Thewet
ani malmar ket s hav er eopened,and peopl e
hav e st art ed buy ing bat s,dogs,cat s,bi r
ds,
scor pions,
badger s,rabbi ts,
pangol i
ns( scalyant eat ers),minks,
soup f rom pal mci v
ct ,ostriches, hamst ers,
snappi
ng
tur
tl
es,
ducks,
fi
sh,
Siamesecr
ocodi
l
es,
andot
her
i
c›1f
li
rtt
›I
.\l
i—Co\
(..
:-‹
. )
.be ci
al
count
ri
eshav
epi
OVl
dedr
ecommendat
ionst
Othei
r
peoplet
ravelingtoChina(8S, 89).
Compar edtothe
prev
iouscor onav i
rusoutbr eakscausedbySARS-
CoVandMERS- CoV, t
heeffi
ci encyofSARS-CoV-
2human-to-humant r
ansmi ssionwast houghtt obe
l
ess.Thisassumpt i
onwasbasedont hef i
nding
that
heal
thworker swereaffect
edl essthantheywerei
n
previ
ousout breaksoff at alcoronav i
ruses( 2)
.
Super
spreadi
ng event
s are consi
der
ed t
he mai
n
cul
pri
tfortheext
ensivet
ransmissi
onofSARSand
MERS ( 90, 91) .Almosthalf of t he MERS-
CoVcases r epor t
ed i n Saudi Ar abia are of
secondar yor i
gint hatoccur red through contact
with infected asy mptomat i
c or sy mptomatiC
Indivi
dualsthroughhuman- to-humant ransmission
(92).Theoccur renceofsuper spreadingev entsin
the COVI D-19 out break cannotber ul
edoutunti
lit
s
possibil
i
tyiseval
uat ed.LikeSARSandMERS, COVID-
19canalsoinfectthe lowerr espir
ator yt r
act,with
mi l
dersy mpt oms ( 27).Thebasi cr eproduction
numberof COVI D-19hasbeenf oundt obeint he
rangeof 2.8to3. 3basedonr eal-
timer eport
sand
3.
2to3.
9basedonpr
edi
ctedi
nfect
edcases(
84)
.
ii
ii
clei caci út esii ‘
cst i
lts. i
sor deof they‹ i
údi i
i
oi i.i
l
dischar gecr iteriai nl abor atory -conf innedcases
ofCOVI D-19( 32ó) .
TheCOVI D- 19pandemi cdoesnot hav eanynov el
fact ors, ot her t han t he genet icall
y uni que
pat hogenandaf ti
uherpossi bler eser voir.The
cause and t he l i
kel yf utur e out come ar ej ust
repet itions ofour
prcv iousi nt eract i
onswi t
hf atalcor onav ir
uses. The
onlydi ffer encei st het i
meofoccur r
enceandt he
genet ic di stinct ness oft he pat hogen i nv ol
v ed.
Mut ationsont heRBD ofCoVsf acili
tatedt hei r
capabi lityofinf ectingnewei host s,ther eby expandi n
gthei rreacht Oal l
cor ner sof thewor ld( 85) .Thi sisa
pot ent ialt hreatt ot heheal thofbot hani mal sand
humans. Adv anced st udies usi ngBay esian
phy logeogr aphi c r econst ruction i dent if
iedt he
mostpr obabl eOf iginofSARS- CoV- 2ast hebat
SARS- l
ikecor onav irus,circul atingi ntheRl i
inol ophus
batf ami ly( S6) .
Phy logenet i
canal y sisof 10whol e-genoi ne
sequencesofSARS- CoV- 2showedt hatt heyar e
relatedt ot woCoVsofbator i
gi n,namel y,bat -
SL-
CoVZC45 and bat -SL- CoVZXC2l ,whi ch wer e
reponed dur i
ng 201S i n Chi na ( 17) .I twas
repor tedt hatSARS- CoV- 2hadbeenconf i
rmed
to use ACE2 asan
entr
yrecept
orwhi
leexhi
bit
inganRBDsi
mil
ar
oÎat y picalcl î
nicalmani fest ationst o av oidt he
possi bili
ty of mi ssed di agnosi s. The
ear l
y transmi ssion abi l
i
ty of SARS- CoV- 2
wasf oundt obesi mi lart oorsl ightlyhi ghcrt han
that of SARS- CoV,
reflect ingthat it
coul dbecont rolleddespi teinoder at e
tohi ght iansmi ssibility( 84).
Incr easi ngr epor tsofSARS- CoV- 2i nsewage
and
wast ewat erwar rantst heneedf orfurtherinv est igat io
nduet ot hepossi bilityoff ecal -oraltransmi ssi on.
SARS- CoV- 2 present i n env i
ronment al
compar t
ment ssuchaSSOi landwat erwi llf inal ly
endupi nt hewast ewat erandsewagesl udgeof
treat mentpl ants( 325) .Ther ef ore,wc hav et o
reev aluat et hecur rentwast ewat erandsewage
sludge treat ment
procedur esandi ntroduceadv ancedt echni quest hat
arespeci f
icandef f
ect iveagai nst SARS- CoV- 2.Si nce
ther ei sact ivesheddi ng ofSARS- CoV- 2i nt he
stool , t he pr ev al enceof i nfectionsi n a
l
ar gepopul ationcanbest udi edusi ngwast ewat er -
based epi demi ol ogy . Recent ly, r ev er se
transcr iption-quant itative PCR ( RT-qPCR)was
used t o enumer atet he copi es of SARS- CoV- 2
RNA concentr
ated fr
om wast ewat
ercol l
ect
ed
fr
om a wastewatertreatment
plant(327).The
cal
culat
ed v i
ral RNA copy number s
deter
minet
henui
nberof
infect
edi
ndivi
dual
s.The
4,l
7t J,
424casc» sand287, 3'?9deat hsaci ‘
osst he
glole.Ther ei s an ur gentneed f ora r at i
onal
internat ionalcampai gn agai nstt he unheal thy
foodpr acticesofChi nat oencour aget hesel lers
to i
ncr ease hygieni c
foodpr acti
cesor closet hecr udeliv e-deadani mal
wetmar ket s.Ther ei sa need t o modi f
yf ood
policiesatnat i
onal andi nt ernational levelst oav oid
further li
fet hr eat sandeconomi cconsequences
from anyemer gingori eemer gingpandemi cdue
tocl oseani lnal -humani nt eraction( 2b5) .
Event houghi ndiv i
dual sofallagesandscxesar e
suscept ibl
et o COVI D-19,ol derpeopl ewi th an
under lyingchr oni cdiseasear emor elikelytobecome
sev erel yinfect ed( 50).Recent l
y ,indiv i
dual swi th
asy mpt omat i
cinf “ectionwer eal sof otindt oactas
asour ceofi nf ect i
ont osuscept ibleindividual s(S1) .
Bot ht heasy mpt omat icandsy mpt omat icpat i
ent s
secr ete si mi l
arv irall oads,whi ch indi catesthat
thet r
ansmi ssi oncapaci tyofasy mpt omat i
cor
mi nimal l
ysy mpt omat ic pat ient si sv eryhi gh.
Thus, SARS- CoV- 2t r
ansmi ssioncanhappenear l
y
i
nt hecour seofi nfect ion( 52) .At ypicalcl inical
mani f
est ationshav eal sobeenr epor t
edi nCOVI D-
19 i n whi ch t he onl yr eporting sy mpt om was
fat
igue.
Suchpati
ent
smay
lackr
espi
rat
ory
signs,
suchas
‹
ii
i113i
oll
l
JCâI
HHdOLf
£111\
lNf
I1*ol
C'O\
UI-
lJThe
t

Chinesegov ernmenti sencour agi ngpeopl et of eel

theycanr eturntonor i
nalcy. However ,
thiscoul dbe a
ri
sk,asi thasbeenment ionedi nadv i
sor iest hat
peopl eshoul dav oidcont act withlive-deadani mal s
asmuchaspossi ble,asSARS- CoV- 2hasshown
zoonot icspi l
lover .Addi tional l
y, wecannotr uleout
thepossi bil
ityof newmut ationsi nt hesamev irus
beingcl oselyr elatedt ocont actwi thbot hani mal s
and humans att he mar ket( 284) .In Januar y
2020,
ChinaimFosedat empor ar ybanont hesal eof li
v e-
deadani mal sinwet mar ket s.Howev er ,
now
hundr edsof such wet mar ketshav ebeenr eopened
wi t
houtopt imizing st andar df ood saf et y and
sanitati
onpr actices( 2b6) .
WithChi nabei ngt hemostpopul atedcount ry
inthewor l
dandduet oitsdomest icandi nter national
foodexpor tationpol icies,t hewhol ewor ldi snow
facingt hemenaceofCOVI D-19,i ncl udingChi na
it
self.Wetmar ket sofl i
v e-deadani mal sdonot
mai ntain st ri
ctf ood hy gienic pr actices.Fr esh
blood spl ashesar epr esentev erywher e,ont he
floorandt abletops, andsuchf oodcust omscoul d
encour age manypat hogens t o adapt ,mut ate,
and j ump t he speci es bar ri
er.As a r esul t
,t he
whol
e wor
ld is suf
fer
ingf
romnov
elSARS-
CoV-
2,
wit
hmor
ethan
pat hogeni ci tyof avirusisof t
enassoci atedwi th
lower transi ni ssibil
ity .
Compar edtoemer gingvir
use
sl ikeEbol av i
rus,av i
anH7N9,SARS- CoV,and
MERS- CoV, SARS- CoV- 2 has r elativelyl ower
pat hogeni city and moder ate t ransmi ssibil
ity
(15) .
The r isk of deat h among i ndivi
duals
inf ect ed wi t
h COVID-
19wascal cul atedusi ngtheinfection f atali
ty r i
sk
(IFR) .TheI FRwasf oundt obei nt her angeof
0.3%t o0. 6%,whi chi scompar ablet ot hatofa
pr ev i
ousAsi ani nfluenzapandemi c(1957t o1958)
(73, 277) .
Not ably ,t he r eanal ysi
s of t he COVI D-19
pandemi ccur vef rom t heiniti
alcl ust erofcases
poi nt ed t o consi der able human- to-human
transmi ssion.I ti s opi ned t hatt he exposur e
hist ory of SARS- CoV- 2at t he Wuhanseaf ood
mar ket origi nat ed f
rom huiii
an-to-human
transmi ssion r ather t han ani mal -
to-human
transmi ssion ( 74) ;howev er,i nl ight of t he
zoonot icspi l
lov erinCOVI D-19,istooear lytofully
endor se t his i dea ( 1). Followi ng t he i nit
ial
i
nf ect i
on,human- to- human t r
ansmi ssion has
beenobser v edwi thapr eliminar yr eproduct i
on
number( Rd)est imat eof1. 4t o2. 5( 70,75) ,and
recent
lyiti
sestimatedtobe2.24t
o3. 58(76).I
n
anotherst
udy,
theaverager
epr
oduct
ivenumberof
Anal ysi s of t he i ni
tial cl uster ‘ of i i
ifeciiOl is
suggest s t hat t
he i nfect edindividualshad a
commonexposur e poi nt ,a seaf ood mar ket i n
Wuhan,HubeiPr ov i
nce,Chi na ( Fig.6) .The
rest aurant s oft his mar ketar e wel l
-known f or
prov iding di fferent t ypes of Wi ld ani mal sf or
humanconsumpt ion ( 7I)
. The Huanan Sout h
Chi na Seaf ood Mar ketal so sel l
sl ive ani mal s,
suchaspoul try,bat s,snakes, andmar mot s(72) .This
mi ghtbe t he poi ntwher e zoonot i
c( animal -
t o-
human) transmi ssion occur red (71) .
AlthoughSARS- CoV- 2isal l
egedt ohav eor iginat ed
from an animal host (
zoonot ic
origin) withfurther human- to-human t r
ansmi ssi on
(Fig.6) ,thel ikelihoodoff oodbor net r
ansmi ssi on
shoul d ber ul ed outwi t
hf urt
heri nvestigat i
ons,
since i
t is a l
atent possi bility
(1).Addi tionally,other potent ialandexpect edrout es
woul dbeassoci atedwi thtr ansmi ssi
on, asi not her
respi ratoryviruses, by di
rect cont act ,
suchasshaki ng
cont ami nated hands,orby di rectcont actwi t h
cont ami nated sur faces ( Fig.6) .St il
l,whet her
blood
transf usi onandor gant ranspl antation( 276),aswel l
astransplacentalandper
inat
alr
out
es,
arepossi
ble
routesforSARS- CoV-
2transmi
ssi
onneedstobe
detennined(Fig.6).
 associaictl
itl
isc› ci'
c cct H1t ›i
Tlici
inaacts globally
duetot hesuddeni nterruptionofgl obaltradeand
supplychainst hatf
orcedmul tinationalcompani esto
makedeci si onst hatledt osi gnifi
canteconomi c
l
osses( 66) .Ther ecentincr easei nt henumberof
confi
rmedcr iti
call
yillpatientswi thCOVI D-19has
alr
eadysur passed t he int ensiv e care suppl i
es,
l
imiti
ngi ntensi v
ecar eser v i
cest oonl yasmal l
porti
onof critical
lyil
l
patients( 67).Thismight also
havecont ributed tot hei ncreased casef atal
ity
r eobser
at vedi ntheCOVI D- 19out break.

Viewpoi
ntonSARS-CoV2Transmi
ssi
ons
Spread,andEmer
genceSARS-CoVnce

The nov elcoronav i

ruswas i dent ifi
ed wi t
hinI
mont h (25 day s) of t he out break. Thi s i s
i
mpr essi
velyf astcompar edt othet imet akent o
i
dentify SARS-
CoVreportedinFoshan,GuangdongPr ovince,
China
(125 day s) ( 6S). I mmedi ately af ter t he
confi
rmationofv iral
eti
ology ,theChi nesevir
ologists
rapi
dlyrcleasedt hegenomi csequenceofSARS-
CoV-2,whi chplayedacr ucialroleincont r
oll
ingt he
spreadofthi
snewlyemergednovelcoronav
irusto
otherpar
tsofthewor
ld(6i
9).Thepossi
bleori
ginof
SARS-CoV-2andthef
irst
modeof
 Intheunr oot edphy logenetictreeofdi ff
erent
bet acor onav irusesbasedont heSpr ot ein,v i
rus
sequencesf rom di ff
er entsubgener agr oupedi nt o
separ at ecl ust ers.SARS- CoV- 2sequencesf r
om
Wuhan and ot hercount r
ies exhibit
ed a cl ose
relationshi pandappear edi nasi ngleclust er( Fig.
l
) .TheCoVsf rom t hesubgenusSml ›ecov ii
us
appear ed j ointlyi nSpl i
tsTreeand di videdi nt o
three subci ust ers,namel y. SARS- CoV- 2,bat -
SARS- l
ike-CoV( bat-SL-CoV) ,andSARS- CoV( Fig.
1).I n t he case of ot her subgener a,like
Her hec' ov i
ros,alloft hesequencesgr oupedi na
singlecl uster,wher easi nEmhecov i
rus,di ff
erent
speci es,compr isedofcani ner espir
at oryCoVs,
bov ineCoVs,equi neCoVs,andhumanCoVst rain
(OC43) ,gr oupedi nacommoncl uster.Isol atesi n
the subgener a Nobecov or
u.s and
Hibecov iruswer efoundt obeplacedsepar at elyaway
from ot her repor ted SARS- CoVsbutshar ed abat
origin.

CURRENTWORLDWI
DESCENARI
OOF
SARS-
CoV-
2

Thi
snov
elv
irus,
SARS-
CoV2,
comesundert
he
subgenus Sar
becov
irus of
theOr
thocor
onav
iri
nae
s
uub
si
nfami
gt l
hyandi
eMc eA s
lie
gn t
nsire
ol
fy
tdi
w af
f
rer
enen
o t
gf
r
io
aimt
n,ihve
lv
i
ci
ir
'use
ct hse
simi l
ar i
tybet weent henov elSARS- CoV- 2isol ates
wasi nt herangeof 99. 4%t o100%. Amongt heot lier
Ser hecov irusCoV sequences,t henov elSARS-
CoV-
2sequencesr ev eal edthel iighestsimi l
ar it
y t
obat -SL-
CoV,wi t
h nucl eot i
de per cent i denl ityr anges
bet ween85. 12 and
89.65%. Meanwhi l
e,ear lierrepon dSARS-
CoVsshowed70. 6t o 74. 9% si mi l
ar i
t yt o SARS-
CoV- 2 at t he nucl eot ide l evel. Fur tl
ier,t he
nucl eot i
deper dentsi mi lari
tywas55. 4%,45. 5%
to47. 9%,4ó. 2%t o46. 60/,and45. 0' /
to46. 3%t o
theot herf oui’subgener a,namel y,Hi l›
ec’ov irus,
Nohecov i
iia,
Mcr he‹ ’
ov irus, and Embecov irus,
respect i
vely. The per cent si milarityi ndex of
current out break i sol at es i ndicat es a cl ose
relationshi pbet weenSARS- CoV- 2i solatesand
bat - SL- CoV, i ndi cat ing a common or igin.
Howev er,par ti
cul arpi ecesofev idencebasedon
further coinplete genoi ric anal ysis of cur rent
i
sol atesar enecessar yt odr aw anyconcl usi ons,
althoughi twasasccr tainedt hatt hecur r
entnov el
SARS- CoV- 2i sol ates bel ong t ot he subgenus
Sur hecov iito i n t he di veise r ange of
betacoronavir
uses.Thei rpossibleancestorwas
hypothesized t
o be fr
om bat
CoVstrains,
wher ei
nbatsmi ght
havepl
ayedacruci
alr
ol
e
i
n t
hisclassotv
iruses.
 TheNpr oteinofcoi 'onav irusi si i
iulti
pur pose.
Among sev eralf unct ions,i tpl aysar olei H
compl ex f ormat ion wi th t he v iral genome,
facili
tatesMpr oteininter actionneededdur ingv i
ri
on
assembl y,
and enhances t he t ranscr ipti
on
effici
encyoft hev ius(
r 55,56) .Itcont ainst hree
highlyconser v edanddi sti
nctdomai ns,namel y,
anNTD,anRNA- bindingdomai noral i
nkerr egion
(LKR) , anda CTD (57) TheNTDbi
. nds
witht he3’endof thev ii•
a1genome, per haps v i
a
electrostatici nteract i
ons,andi shi ghl ydi verged
bot hi nlengt handsequence( 5S).Thechar ged
LKRi sser i
neandar gi
ni ner ichandi sal sok nown
ast heSR( serineandar ginine)domai n( 59) .The
LKRi scapabl eofdi r
ecti nter actionwi thi nv i
ti
o
RNA i nteraction and i sr esponsi blef or cel l
signal ng(
i 60,61) .Italsomodul at estheant ivi
raJ
response of t he host by wor king as an
ant agonist f or i nterfer on ( IFN) andRNA
i
nt erferencc(62) . Compar edt o t hat of SARS-
CoV, theNpr oteinof SARS- CoV- 2 possess f i
ve
ami no aci d mut ati
ons,wher et wo ar ei nt he
i
nt ri
nsicallydi sper sedr egi on( IDR;posi tions25
and26) ,oneeachi nt heNTD( positi
on103) ,LKR
(posit i
on217) ,andCTD( posi ti
on334)( I
6) .
nspsandAccessor
yPr
otei
ns
MProtei
n
TheMprot
eini
sthemost
abundant
vir
alprotei
n present
i
nt hev i
rionpar t
icle,givingadef ini
teshape t ot he
viralenv elope( 45) .Itbindst ot henucl eocapsi d
andact sasacent ralor ganizerofcor oii
av i
rus
asser nbly( 49).Cor oii
av i
rus M pr oteins ar e
highly di verse i n ami no aci d cont ents but
mai ntain ov eral
l st ructural simi l
ari
ty wi t
hin
differentgener a( 50) .TheM pr otei
nhast hree
transmembr ane domai ns,f lanked bya shor t
ami not er minusout sidet hev i
ri
onandal ong
car box ytermi nusi nsidet hevi r
ion(50) .Overall
,
the v i
ral scaf f
old i s mai ntained by M- M
i
nt eraction.Ofnot e,theM pr oteinofSARS- CoV
-2 does not hav e an ami no aci d
subst it
utioncompar edt ot hatofSARS- CoV( 16).

EPr
otei
n
Thecoronavi
rusEprot
einist
hemosteni
gmat i
c
andsmallestoft
hemajorst r
uctur
alpr
oteins(5l)
.I
t
playsar nul
ti
functi
onalroleinthepathogenesi
s,
assembly,andr el
easeoft hevir
us(52).Itisa
 li
smal ntegr
almembr anepolypeptidethatacts
asavi
ropori
n(i
onchannel
)(
53)
.Theinacti
vat
ionor
cl
assl
›iialI
ldl
4Sll
3cir
biaBcpi ’
r›
tci
n.Thesixcoll
l
ii
s
abundantSprotei
nv ariesfrom l,
1ó0ami noaci
ds
(I
BV,infect
ious bronchiti
sv ir
us,i n poul
tr
y)to
1,
400
ami noaci ds(FCoV, fel i
necor onav irus)(43) .
Itl
ies i n
at rimeront hev irionsur face,gi v i
ngt hev i
riona
cor onaorcr own- l
ikeappear ance.Funct ional l
yi t
i
s
requi rcdf ortheent ry oftheinf ect i
ousv i
ri
onpar ticlesi
ntot hecel lt
hr oughi nt eractionwi thvar i
ous host
cel l
ul arrecept or s(44) .
Fur thermor e,i
tact sasacr i
ticat factorforti
ssue
tropi sm andt hedet er minat ionofhostr ange( 45) .
Not abl y, S pr ot ein i s one of t he
vitaliini
nunodoi ninantpr ot ei nsofCoVscapabl e
ofi nduci nghosti mmuner esponses( 45) .The
ect odomai nsi nal lCoVsSpr oteinshav esi mi l
ar
domai nor gani zat i
ons,di v i
dedi ntot wosubuni ts,
SIand52( 43) .Thef ir
stone,S1,hel psi nhost
recept orbi ndi ng,whi let he second one,S2,
account sf orf usion.Thef or mer( S1)i sf ur ther
divided i ntot wo subdoi nai ns,nai i
iely,t he N-
termi na1domai n( NTD)andC- termi naldomai n
(CTD) . Bot h of t hese subdoi uains act as
recept or-bindi ng domai ns,
i
nt er actinget fi
ci entlywithv ar i
oushost recept ors(45)
.
TheSl
CTDcontainst
hereceptor
-bindi
ng moti
f
(
RBM).ln each coronavirusspi keprotei
n,the
t
ri
meri
cS1locatesit
sel
fontopofthetr
imeri
cS2
(4U,
1I )
.
Cor onav i
rus genomes and subgenomes
encode
sixORFs( 3I).Themaj ori
ty oft
he5' endisoccupi edby
ORF1a/ b,whi ch pr oduces16 nsps.The t wo
polypr oteins, ppIaandpp1ab,ar eini
ti
ally pr oduced
fromORF1a/ bbya—1f raineshiftbet weenORFl a
andORFl b(32) .The v i
rus-encodedpi ot easescl eav e
poly prot einsi ntoi ndividualnsps( mai npr otease
[Mpr o],cl iymot rypsin-l
ikepr otease[ 3CLpr o] ,and
papai n- l
ikepr ot eases[ PLPs] )( 42).SARS- CoV- 2
alsoencodest hesensps, andt heirfunct i
onshav e
been el ucidat ed r ecent ly( 31) .Remar kably,a
differencebet weenSARS- CoV- 2andot herCoVs
i
st he i dent if
ication ofa nov elshor tput ative
proteinwi thint heORF3band,asecr etedpr otein
wi t
h an al phahelixandbet a-
sheet wi thsi xstrandsencodedby ORFS( 3l )
.
Coronavi
rusesencodef ourl
najorstr
uctur
al
protei
ns,
namely,spi
ke(
S),
membrane(
M) ,
env
elope
(E),andnucl
eocapsid(N),whi
charedescr
ibedin
detail
bel
ow.

SGl
ycopr
otei
n
Cor
onav
irusSpr
otei
nisal
arge,
rnul
ti
funct
ional
cl
assI
vi
ral
tr
ansmembr
anepr
otei
n.Thcsi
zeof
thi
s
 l
eased on wool
ecuUm cl
i
.i
i’
act
ci’
i
zat
ion, SAI
NS-
CoV- 2 is consi der eda new
Bet acoronavi rus
belongi ngtot hesubgenusSai becov irus(3).Af ew
other cri
t i
calz oonot i
cv iruses( MERS- rel
at edCoV
andSARS- relatedCoV) belongt othesamegenus.
However ,
SARS- CoV- 2wasi dent ifi
edasadi stinct
vir
us based ont heper centi dent itywi thot her
Bet acoronavi rus;conser vedopenr eadi ngframel a/b
(ORFI a/ b)isbel ow90% i dent it
y ( 3) .Anover all
80% nucl eot idei dent it
ywas obser v ed
betweenSARS- CoV- 2 and t he or lginal SARS-
CoV,al ongwi th89%i dent ity
withZC45andZXC21SARS-
relatedCoVsof bats(2,31,36) .Inaddi tion,82%
i
dent i
tyhasbeenobser v edbet weenSARS- CoV- 2
andhumanSARS- CoVTor 2andhumanSARS- CoV
BJ0l 2003( 31) .Asequencei dent i
tyofonl y5I.8%
wasobser vedbet weenMERS- relatedCoVandt he
recent l
yemer gedSARS- CoV- 2(37) .Phy l
ogenet ic
anal ysi
sof thest ructuralgenesal sorev ealedt hat
SARS- CoV- 2iscl osertobat SARS-
relatedCoV. Ther efore,SARS- CoV- 2mi ghthave
ori
gi natedfrom bat s,
whi leother ampl ifi
erhost s
might havepl ay edar ol
ei ndi seaset ransmi ssi onto
humans( 31).Of note,
theothert
woz oonOti
CCOVS( MERS-
rel
atedCoV
andSARS- relat
edCoV)alsoor
igi
nat
edfr
ombat s
(3b,39).
Nev ert
hel
ess,f
orSARSandMERS,civ
et
arrangedi nl icl i
Calsy mmet ry,whi ch r ef l
ect san
atypi cal at tribut einposi t
ive-senseRNAv iruses( 30) .
Theel ect r onmi crogr aphsof SARS- CoV- 2rev eal ed
adiv er ging spher icalout l
inewi thsomedegr ee of
pl eomor phi sm, viri
ondi amet ersv aryingf r
om60t o
140nm, anddl st i
nct spikesof 9t o12nl Ti,
glv ingt he
virust heappear anceofasol arcor ona( 3).
TheCoV
genomei s ar r angedl i
near l
y as5' -l
eader -UTR-
repl icase- struct ur al genes( S-E- M- N) -
3' UTR-
pol y (
A) (32) .Accessor ygenes, suchas3a/ b, 4a/ b,
andt hehemaggl ut i
nin-est erasegene( HE),ar eal so
seeni nt ermi ngl edwi tht hest ruct uralgenes
(30) .SARS- CoV- 2 hasal sobeenf ound
tobear rangedsi mi l
arlyand encodes
sev eralaccessor ypr oteins,
alt houghi tlackst heHE, whi chi Schar acterist icof
somebet acor onav iruses( 31) .
Theposi ti
v e-sense
genomeof CoVsser v esast hemRNAandi s
transl atedt opol ypr oteinIal
l ab( pp1wI ab)(33) .A
r
epl icat ion- transcr ipt i
oncompl ex( RTC) i
sfor medi n
doubl e- membr anev esi cles( DMVs) by nonst nict ural
pr otei ns( nsps) ,encodedby thepol yprotei ngene
(
34) .Subsequent l
y,theRTCsy nthesi zesanest edset
of subgenomi cRNAs( sgRNAs) viadiscont inuous
t
ranscr
ipt
ion(
35)
.
diseaseout breakst hathav enotbeencont rolled
to
dat e,
althoughext ensi veef f
or t
sar ebei ngput i
npl ace
to count ert hisv irus (25) .Thi sv i
rus hasbeen
proposedt obedesi gnat ed/namedsev ereacut e
respiratorysy ndr omecor onav i
rus2( SARS- CoV-
2)byt heI nternat ionalCommi tteeonTax onomy
ofVi r
uses ( ICTV) ,whi ch det ermi ned t he v i
rus
belongst ot heSev er c•
acut eie.spirator ysyndi ome
relatc•d
cor onaviruscat egor yandf oundthi svirusisrelatedto
SARS- CoVs( 2f›)
.SARS- CoV- 2i samemberof
the order Nidov i
r ale.
s, fami l
y
Cor onav i
ridae,subf ami ly Or thocor onnv i
i i nae,
whi ch is subdi vided intofotirgener v
a, i
a
-.
,Alphac’Orotiavir
us,
Bet
acoFOl
lav
irus, Gami
Hff
COr
Onav
il
“t
lS, i
tnd
Del
tacor
onuv ir
us ( 3, 27) . The gener a
Al
phacoronav i
ru.sandBet acoronavi
rusor
igi
natef
r o
mbats,
whieGammncor
l onav i
rusand
Dcl
tac'
oi
onuv ii
its hav e ev olved fr
om bi r
d and
negenepool
swi s( 24, 28,29, 275)
.
Coronaviruses possess an unsegi nented,
si
ngle- stranded, positi
ve-senseRNA genomeof
ar
ound30kb,encl osedbya5' -
capand3'-poly
( A)
tai
l(30).ThegenomeofSARS- CoV-2is29,
891bp
l
ong, wit
h a
G+Ccont entof
38%(31).
Thesevi
rusesare
encir
cledwit
hanenvel
opecontai
ningv
iral
showed ef ficacy i nt o m' ti
o st udies;howev er
,
todate,theset reatment shav enotunder goneany
randomiz edani malorhunt ancl inicalt r
ials,whi ch
l
imitt heirpr acticalappl icabili
tyi nt he cur rent
pandemi c( 7, 9,19- 21) .
Thepr esent compr ehensiv ereviewdescr ibesthe
vari
ous f eat ures of SARS- CoV- 2/COVI D-19
causing t he cur rent di sease out breaks and
advances
i
ndiagnosi sanddev elopingv accinesandt her apeutic
s.I
tal so pr ov i
desa br iefcompar ison wi tht he
earl
ier SARS
andMERSCoVs, thev eteri
nar yperspect iveof CoVs
and t hi
s emer ging nov elpat hogen,and an
evaluati
onoft hezoonot icpot ent i
alofsi milar
CoVst opr ov idef easi bleOneHeal thst rategies
forthemanagement ofthisfatalvirus(22-367) .

THEVI
RUS(
SARS-
CoV-
2)
Coronavir
uses ar e posi ti
ve-sense RNA
vir
useshav i
ng anex t
ensiveand pr omiscuous
range of natur
al hosts and af fect mul t
ipl
e
systems (
23, 24).
Coronav i
rusescancausecl
inical
diseasesinhum
anst hatmayex t
endfrom thecommoncol dto
moresev ererespir
atorydiseasesl i
keSARS
and MERS (17,279) .Ther ecentl
yemerging
SARS-CoV-2 has
wrought
havoci
nChinaandcausedapandemi
c
f
rom SARS-
CoV (
7V*
/o si
i
«il
aii
ty)and VLkS-
CoV
(nearly50%)( 17).COVID-19isassociatedwith
affl
ictions of t he lungs in all cases and
gener at ed char act
eri
sti
c chest comput er
tomogr aphy findi such as t
ngs, he presence of
multiplel esions inlung lobes t
hatappearas
dense,gr ound-glass opaque struct
ures that
occasi onally coexi st wi th consol i
dat
ion
shadows( ia)
1 '
I t
iI I
' . i
i
II
tI
c I \<1I
£1t
i1. t
1 II
cII
i
1 I

epi
demi
cs (
l3)
.The i
i
iost coi
i
ini
olisy
ii
ipt
OlJ4S
associ ated wi th COVI D-19 ar ef ever ,cough,
dy spnea, ex pect or ation, headache, andi ny algiaor
fatigue.
Incont rast ,l esscommonsi gnsatt het i
meof
hospi tal admi ssi oni ncludedi ar r
hea, hemopt y sis,
and
shor t nessof br eat h( 14).Recent ly,indi vidual swith
asy mpt omat ici nfect ionswer eal sosuspect edof
transmi tti
ngi nfect i
ons, whi chf ur theraddst ot he
compl exityofdi seaset ransmi ssi ondy nami csi n
COVI D- 19i nf ect ions( 1).Suchef fi
ci entr esponses
requi rei n-dept hknowl edger egar dingt hev i
rus,
whi chcur rent lyi sanov elagent ;consequent ly
,
furtherst udi esar erequi red.
Compar ingt hegenomeof SARS- CoV- 2wi ththat
of t he cl osel yr elated SARS/ SARS- l
ike CoV
rev eal edt hatt hesequencecodi ngf ort hespi ke
prot ein,wi that ot allengt hof1, 273ami noaci ds,
showed 27 ami no aci d subst i
t utions.Si x of
these subst itutionsar eint heregi onof t
her eceptor-
bindi ng domai n ( RBD) , and anot her si x
subst itutions ar ei nt he under pi nningsubdomai n
(SD)( 16) .
Phy logenet i
canal y seshav er eveal edt hat
SARS- CoV- 2i Scl osel yr elated( 88%si mi larity
)t o
two SARS- like CoVs
der
ivedf
lowbat
SARS—l
i
keCoVs(
bat
—SL—
on l lMar ch 2020,t heydecl ar ed itapandei nic
situation.Atpr esent,weai '
enoti naposi ti
ont o
effect i
v ely t reat COVI D- 19, si nce nei ther
appr ov edv acci nesnorspeci ficant iviraldni gsf or
treatinghumanCoVi nf ect ionsar eav ai l
able( 7-9).
Mostnat i
ons ar e cur r
ent l
y maki ng ef fort st o
prev enlt he f urtherspr cadi ng of t
his pot ent i
al l
y
deadl y virus by
i
mpl ement ingpr eventi
veandcont r
ol st
rategies.
I
ndomest icani mal s,inf ectionswi thCoVsar e
associ at edwi t
habr oadspect ruinofpat hol ogi cal
condi tions.Apar tf r
om i nf ect i
onsbr onchi ti
sv irus,
caniner espi r
at oryCoV,andmousehepat i
ti
sv irus,
CoVs ar e pr edomi nant ly assOCi £itCd wi th
gast roint est i
naldi seases( 10) .Theemer genceof
nov elCoVsmayhav ebecomepossi blebecause
of mul tipleCoVsbei ngmai nt ained
i
nt heirnat ur al
host , whi chcoul dhav efav ored
thepr obabi liyOï
t geneticr ecombi nation( 10) .Hi gh
genet icdi versityandt heabi li
tyt oinfectmul tiple
host speci es ar e a r esult of hi gh-
frequency mut ati
onsi nCoVs,whi choccur duet o
the i nst ability of RNA- dependent RNA
polymer ases al ong wi th hi gher r ates of
l
iomol ogous RNAr ecombi nat ion ( 10, 11) .
Identi
fying t he or i
gin of SARS-CoV-
2 and
thepathogen's ev ol
uti
on wi l
lbe hel pf
ulf
or
diseasesurvei
l
lance(
12)
,devel
opmentof
Lr
»r›
oa›
i'
ti
scsi
i
iIl
nonut
s .
\US.XI
LII
b.
andCOVI
D-19
Coronav i
r usi nf ectioni nhumansi scommonl y
associatedwi thmi l
dt osev ererespi ratOr ydiseases,
withhighf ev er,sev erei nf l
ammat i
on,cough,and
i
nternalor gandy sf unctiont hatcanev enl eadt o
death( 92) .Mostoft hei dent ifi
edcor onav i
ruses
causet hecommoncol di nhumans.Howev er,
thi
s changedwhenSARS-
CoVwasi dent ifi
ed, pav ingt he
way f
orsev er efor msof thedi seasei nhumans( 22) .
Ourpreviousexper iencewi ththeout br eaksof ot her
coronav ir
uses,l i
keSARS and MERS,suggest s
thatthemodeoft r
ansmi ssi oni nCOVI D- 19as
mainlyhuman- to- humant ransmi ssionv iadi rect
contact,dr opl et s,and f omi tes ( 25) .Recent
studi
es hav e
demonst ratedt hat thev ir
uscoul dr emai nv i
abl efor
hoursi naer osol sandupt oday sonsur faces;
thus,
aerosolandf oi nitecont ami nat i
oncoul dplay pot ent
rol
esi nthet r anslni ssionofSARS- CoV- 2( 257) .
Theimmuner esponseagai nst coronavi r
usi svital
tocont rolandgetr i
doft hei nf ection.Howev er
,
maladjustedi mmuner esponsesmay cont r
ibutet othe
i
mmunopat hol ogyoft he di sease,r esult i
ng i n
i
mpai r
ment of pul monary gas exchange.
Understandi
ngt
heinteract
ionbetweenCoVsand
host
innatei
mmunesy
stemscouldenl
ight
enour
GOfOl
JâVÎ
fUS(SARS-CoV-
2)andSARS-keCoVs, t
l
i he
comparat
ive analy
sis recognized a furi
n-l
ike
cl
eavagesit
eintheSARS- CoV-2Spr ot
einthatis
nissi ngf rom ot herSARS- likeCoVs( 99).Thef ur i
n
-likecl eav agesi t
ei sexpect edt oplayar oleinthel i
fe
cy cleoft hev irusanddi seasepat hogeni ci
tyand
lTllghtev enactasat her apeut ict argetf orf ur i
n
inhi bitors.Thehi ghl ycont agi ousnat ureofSARS-
CoV- 2compar edt othat ofitspr edecessor s mi ght be
ther esul tof ast abili
z ingmut at i
ont hatoccur redi n
theendosome- associ atcd- protein-likedomai nof
nsp2pr otein.
Simi larly,t hedest abiliz i
ngmut ationneart he
phosphat asedoi nainofnsp3pr oteinsinSARS- CoV-
2 coul di ndicat e a pot ent ialmechani sm t hat
differ ent i
atesit f r
om ot her CoVs( 100) . Ev er
thought heCFRr epor tedf orCOVI D- 19i smeager
compar ed t ot hoseof t
he pr evi
ous SARS and
MERS outbr eaks, i thascausedmor edeat hs
thanSARSand MERScombi ned ( 101) . Possi bly
relat cd t ot he v ir
alpat hogenesi si st he recent
findi ngofan832-nucl eot ide( nt)del eti
oni nORF8,
whi ch appear s to
reducet her epl
icat ivefitnessof thevirusandl eadsto
at t
enuat edphenot ypesof SARS- CoV- 2(256) .
Cor
onavi
rusi
sthemost
promi
nent
exampl
eof
a
occui ’dii
'
cctlyt i
onst her escr xoii
’mostt ohumaBs
withoutRBD adapt at i
ons.The batcor onav irus
thati scur r
ent lyinci rcul ati
onmai ntainsspeci fi
c
“poi sed” spi kepr ot eins t hat fäCÎli
tate hui nan
i
nf ect ion wi thout t he r equirement of any
mut at i
ons oi • adapt at i
ons( 105) . Al toget her ,
dif
f er entspeci esofbat scar ryamassi venui nber
ofcor onav i
rusesar oundt hewor ld( l
0fi).
Thehi ghpl asticityi nr ecept orusage.al ong
with t he f easibility of adapt ive mut ation
andr ecombi nat ion, may r esul t in f r
eqt ient
i
nter speciest ransmi ssi onofcor onav ir
usf rom
bat s t o ani mal s and humans ( 106) . The
pat hogenesi s of most bat cor onav i
rusesi s
unknown,as most of t hèse v iruscsar e not
i
sol at ed and studied (4).
Hedgehogcor onav irusHKU3l , aBet acor onuv ii
u’,
hasbeen i dent i
fied f r
om amurhedgehogs i n
Chi na.St udies show t hathedgehogs ar el he
reser voii of Bet u‹ ’oronav irus, and t her e i s
évidenceofr ecoi nbinat ion( 107) .
The cur rent sci ent i
ficev i
dence av ailable
onMERSi nfect i
onsuggest sthat t
hesigni f
icant reser
voirhost ,aswel last heani malsour ceofMERS
i
nf ect ion in humans,i st he dr omedar ycai nels
(97)
.
Thei
nfect
eddr
oinedar
ycar
net
smay
not
showany
pot
ent
iali
'
iskf
o’t
hei
‘
eei
i
iei
’
genceof
’SA RS-
CoV
i
nfect
ion f
rom the vi
ruses thatare cur
rent
ly
ci
rcul
ati
ngi
nthebatpopulat
ion(l
05)
.

CLINI
CALPATHOLOGYOFSARS-
CoV-
2
(COVI
D-19)
Thedi seasecausedbySARS- CoV- 2isal so
namedsev erespeci f
iccont agiouspneumoni a
(SSCP) ,Wuhanpneumoni a,and,recent ly,
COVI D-
19( I10) .Compar edtoSARS- CoV,SARS- CoV- 2
hasl esssev erepat hogenesi sbuthassuper i
or
transmi ssion capabi l
ity
,as ev i
denced by t he
rapidlyi ncreasi ngnumberofCOVI D-19cases
(l
11) .Thei ncubat i
onper i
odofSARS- CoV-2i n
fami l
ial cl ust ers was f ound t o be 3 t o
6day s(112) .The mean i ncubat ion per i
od of
COVI D-l9wasf oundt obe6. 4day s,rangingf r
om
2.1t o111day s(113).Amonganear lyaffected
groupof 425pat ients,59y ears was t he medi an
age,of whi ch mor e mal es wer e af fected
(114).SimilartoSARSandMERS, thesev eri
tyofthis
nCoVi shi ghi nagegr oupsabov e50y ears( 2,
115) .
Sy mpt oms of COVI D-19 i nclude f ever,
cough,my algiaorf at
igue,and,l esscommonl y,
headache,hemopt ysi
s,anddi arrhea( 116,252) .
Compared t o t he SARS-
CoV-
2-i
nfect
ed
pat
ient
sinWuhandur
ing
sy
inai
our
siv
crcnot
icedi
i
ii
hosej
i
ii
tl
Cl4t
Sll
4il
l
1ll
‘
C.
infect edby human- to-humant ransmi ssion( 14) .
Thei ni t
ialtrendssuggest edt hatt hemor talit
y
associ at edwi t
hCOVl D-l
9wasl esst hant hatof
pr ev i
ousout breaksofSARS( 101) .Theupdat es
obt ai ned f rom count ri
es l i
ke Chi na, Japan,
Thai land,and Sout h Kor ea i ndicat ed t hatt he
COVI D- 19pat ients had relat iv
el y mi l
d
i
nani Gest ati
ons compar ed t ot hose wi thSARS
andMERS( 4).Regar dlessoft hecor onav irust ype,
i
mmunecel l
s,likemastcel l
s,t hatar epr esenti n
the submucosa of t he respi rator y
tract andnasal cav i
tyareconsi deredt hcpr i
mar y
bar rieragai nstt hisv irus(92) .Adv ancedi n- depth
anal y sisoft hegenomehasi dent if
ied350ami no
aci d subst ituti
ons bet ween t he ami no aci d
sequencesofSARS- CoV-2andt heSARS/ SARS-
l
ike cor onav ir
uses.These di f
fer ences i nt he
ami no acid
sequencesmi ghthav econt ri
but edt othedi fferencei
nt hepat hogeni cdi v ergenceofSARS- CoV- 2( 16) .
Fur therr esear ch i sr equired t o ev aluat et he
possi bl edi fferencesi nt ropism,pat hogenesi s,
andt ransmi ssionoft hisnov elagentassoci ated
wi tht hi schangei nt heami no aci d sequence.
Wi tht hecur r
entout breakofCOVI D-19, t
her ei san
expectancy of a
si
gnifi
canti
ncr
easeint
henumberofpubl
ished
st
udiesaboutt
hisemergi
ngcoronavini
s,asoccur
red
hast hepot ent ialt oi nf ecthumans.Howev er,they
mayshedMERS- CoVt hr oughmi lk,ur ine,f eces,
andnasal andey edi schar geandcanal sobef oundi n
ther aw or gans( 10b) .I nast udyconduct edt o
ev aluat et hesuscept ibil
ityofani malspeci est o
MERS- CoVi nf ect ion,l l
amasandpi gswer ef ound
to be suscept ible,i ndi cating t he possi bil
ityof
MERS-CoV ci rcul ationi nani malspeci esot her
thandr oi
nedar y camel s( 109) .
Fol lowi ngt heout bi'eakof SARSi nChi na,SARS-
CoV- likev iruseswer ei sol ated f rom Hi mal ay an
pal m civ ets Puguma furruio) and
raccoondogs{ Ny tcr t
• ti
te.v pi
ocy onoi Je. v
foundi na
l
iv e-ani mal mar ket i n Guangdong, Chi na.
Theani malisol atesobt ainedf r
omt helive-
ani mal mar ketr et aineda29- nucl eot i
desequence
thatwas notpr esenti n mostoft he hul nan
i
sol ates (7b) . These
findi ngswer ecr i
tical inident i
fying t hepossi bil
ityof
i
nt er speci es t ransmi ssi on i n SARS- CoV. The
higher
div ersi t
yandpr ev alenceof bat coronav irusesinthis
regi oncompar edt ot hosei npr eviousr epor t
sindicate
a host /pat hogen coev olut i
on. SARS- li
ke
cor onavi rusesal sohavebeenf oundci rculati
ngint he
Chinese horseshoe bat( Rhinolophus sini
cus)
populat
i Thei
ons. ii
ri
lr av
oandi ivostudiescar
ri
ed
 l
'
csul
i
s i
l
i al
i cpi
ti
c l
i
i1c by j
uli
i p11a t
he

m’
0
0
m
so—cal ledspeci esbarri
er(257) .
Thehost spect r
umof Cor onavirusincreasedwhen
anov el cor onav i
rus, namel y
, SW1, was
recogni zedi nthelivertissueof acaptivebel ugawhal e
{Del pli
inapt crtisl eucas) 138).Inr ecentdecades,
sev eralnov elcor onav iruseswer ei dent i
fiedf r
om
differentani malspeci es.Bat scanhar bort hese
viruseswi t
houtmani fest i
nganycl inicaldi sease
butar eper sist entl
yi nf ected( 30).Theyar et he
onl ymammal swi tht hecapaci tyforsel f-power ed
fl
ight , whi ch enabl esthem t o mi gratelong
distances, unl i
ke l and mammal s. Bat s ar e
disti'
ibutedwor ldwideandal soaccountf orabout
a fift
h of al
l mammal i
an
speci es(6) .
Thi smakest hemt heideal r eser voi r
host
formanyv ir
alagent sand al so thesour ceof
nov elcor onav ir
usest hathav ey ett obei dent i
fied.
Ithasbecomeanecessi t
yt ost udyt hedi versity
ofcor onav ir
usi nl hebatpopul at i
ont o pr event
futur e out breaks t hatcoul djeopar dize l ivestock
andpubl i
c
heal th.Ther epeat edout breakscausedby bat -
or i
gin
cor onav i
ruses cal ls f or t he dev elopment of
efficient mol ecul arsur veil
lance st r
at egies f or
study ng Bet
i ncor onav iiu.s among ani mal s( 12),
especiall
y i
n
thefi
fi
ioofophosbatf
amil
y(86)
.Chinesebat
shave
highcommer ci
alv
alue,
si
ncetheyareusedi
n
mi nimum si gns and sy mpt oms ( 82) .Anot her
study ,conduct edinSout hKor ea, relatedt oSARS-
CoV- 2v iralload, opinedt hatSARS- CoV- 2kinet ics
wer esi gni f
icantlydi fferentf rom t hoseofear li
er
reported CoV i nfect i
ons,i ncl uding SARS- CoV
(253) .SARS-CoV- 2t ransmi ssioncanoccurear l
y
i
nt hev irali
nfecti
onphase;t hus,di agnosi ngcases
and i
solation
attempt sf orthi
sviruswar rantdif ferentstrategiestha
nt hoseneededt ocount erSARS- CoV.St udiesar e
required t o establish any cor rel
at i
on bet ween
SARS-CoV- 2v i
rall oad and cul ti
vabl ev i
rus.
Recogni zing pat ient s wi th f ewer or no
sympt oms, along
withhav ingmodest det ectablev i
r alRNA i n t he
orophar y nxf or5day s,indicat est her equi r
ement
ofdat af orassessi ngSARS- CoV- 2Pansmi ssi on
dynami csandupdat i
ng the screeni ng
procedur esintheclinics( 82).
sunilationrccI i
cesneedsi t›I egi en dueci rp1i:i
si s
(249- 252) .Fut ureexpl orat ivcr esear chneedst o
be conduct edwi thregar dto the fecal -
oralt
r ansmi ssion of SARS- CoV- 2,al ong wi th
focusi ngonenv i
ronment alinv est i
gationst of ind
outift hisv i
ruscoul dst ayv iabl ei nsituati
onsand
atmospher esf acil
it
at i
ng such pot entr out esof
transmi ssion. The cor relat ion of f ecal
concent r
ationsofv i
ralRNAwi thdi seasesev er ity
needst obedet ermined, alongwi thassessi ngt he
gastr ointest i
nalsy mpt omsandt hepossi bi l
ityof
decalSARS- CoV- 2 RNA det ect i
on dur ing t he
COVI D- 19 incubat i
on period or
conv alescencephasesof t
hedi sease( 249- 252) .
The l ower r espi rator y t ract sampl ing
techni ques,l ike br onchoal v eol ar lavage f luid
aspirat e, are
consi der edtheidealclinicalmat erials,
ratherthant he
throat swab, duet ot heirhi gher positiver
ateont he
nuclei caci dt est(I45) .Thedi agnosi sofCOVI D-
19canbemadebyusi ngupper -r
espi r
atory-tract
speci menscol l
ectedusi ngnasophar yngealand
orophar yngealswabs.Howev er ,theset echni ques
areassoci atedwi t
hunnecessar yriskst oheal th
carewor ker sduet ocl osecont actwi t
hpat i
ent s
(152) .Si milarly,asi ngl epat ientwi thahi ghv iral
l
oad was r eposed t
o contami
nate an ent
ir
e
endoscopy r
oom by
sheddi
ngthevi
rus,
whi
chmayr
emainvi
abl
efor
at
tobect H1f ii
’
ii
ictliIthei’
cspinatoi
’yti
'
aciasairatcoi’
blood sampl es t est posi t
ivef or SARS- CoV- 2
nucleicacidusi ngRT- PCRorbyt heidentif
ication
of SARS- CoV- 2 genet icsequence i n
respirat
or y
tractaspi r
ateorbl ood sampl es (50).
Thepat ientwi llbeconf ir
medascur edwhent wo
subsequent or al swab r esults ar e negat ive
(153).Recent l
y,thel iv
ev ir
uswasdet ectedi nt he
self-
collected sal iv
a ofpat i
entsi nfected wi th
COVI D-19. These f i
ndings wer e conf ir
mat ive
ofusingsal ivaasanoni nvasi vespecimenf ort he
diagnosi s ofCOVI D-
19 inf ecti
on in suspect ed
i
ndividuals( l52) .Ithasal sobeenobser vedt hat
the i nit
ial scr eening of COVl D-19 pat i
ent s
i
nf ect
edwi thRT- PCRwaygi venegat iver esults
even i ftheyhav e chestCT f i
ndings t hatar e
suggest i
v eofi nfection.Hence,f ort heaccur at e
diagnosisofCOVI D-19,acombi nationofr epeated
swab tests usi
ng RT-
PCRandCTscanni ngisrequiredtopr eventthepossi bi
l
ity of f alse-negative i '
esul t
s dur ing di sease
screening( l54).RT- PCRi st hemostwi delyused
testfordi agnosi ngCOVI D- 19.Howev er,ithas
some si gni fi
cantl imi t
ati
ons f rom t he cl i
nical
perspectiv e,si nce i twi l
lnotgi ve any cl ar i
ty
regardingdi seasepr ogression. Dropletdi git
alPCR
(ddPCR) can
beusedf
ort
hequant
if
icat
ionof
vir
all
oadi
nthe
saml
esobt
ainedf
roml
ower t
ract
s.
uninI'
ect edpat i
ent sandheal thcarewor kers( 259) .
Recent ly,itwas f ound t hatt heanalswabsgav e
mor eposi ti
ver esul t
st hanor alswabsi nthel ater
stagesofi nfect i
on( 153) .Hence,cl i
nicianshav et o
be caut ious whi l
e di schar ging any COVI D- 19-
i
nf ectedpat i
entbasedonnegat i
veor alswabt est
results due I o t he possi bili
ty of f ecal -or al
transmi ssion. Ev en though
thev i
ralloadsinst oolsampl eswer efoundt obel ess
than t hose of r espi ratory Sampl es, st ri
ct
precaut ionarymeasur eshav et obef Ol lowedwhi l
e
handl i
ngst oolsampl esofCOVI D-19suspect edor
i
nf ected pat ient s( 151) .Chi ldren infected wi th
SARS- CoV- 2ex perienceonl yami l
dfor m ofi llness
andr ecov erimmedi atelyaf tertreatment .I twas
recent l
yf oundt hatst oolsampl esofSARS- CoV- 2-
i
nf ectedchi l
drent hatgav enegat ivet hroatswab
resultswer eposi ti
vewi thint enday sofnegat ive
results. Thi s coul d r esul ti n the f ecal -or al
transmi ssion of SARS- CoV- 2 i nfect ions,
especi allyi
nchi ldren( 290) .Hence,t opr ev entt he
fecal-oralt ransmi ssionofSARS- CoV- 2,i nf ect ed
COVI D- 19 pat ients shoul d onl y be consi der ed
negat ive when t hey testnegat i
vefor SARS- CoV-
2int
hest
ool
sample.
S/
ti
(Ll
l
lJ,
l
3£âSal
S\¥i
l
bs.
li
bi‘
obi
olJcl
oscopc•
fr‘
ti
sh
biopsy speci mens,phar yngealswabs,f eces,
andbl ood( 246) .
Thepr esenceof SARS- CoV- 2infecalsampl es
has posed gr ave publ i
c heal th concer ns.I n
addi tion t o t he di rect t ransmi ssion mai nly
occur ring v adr
i opletsof sneezi ng andcoughi ng,
ot her r outes,such as f ecal excr eti
on and
env ironment aland f omi te cont aminat i
on,ar e
cont ribut i
ng t o SARS- CoV- 2t r
ansmi ssion and
spr ead( 249- 252).Fecalex cret i
onhasal sobeen
document ed f or SARS- CoV and MERS- CoV,
along wi tht he pot ent ialt o st ay v iablei n
situations ai ding f ocal -oraltr ansmission.Thus,
SARS- CoV- 2 hasev ery possi bili
ty t o be
transmi tted t hrough t his mode. Fecal -oral
transmi ssion of SARS- CoV- 2,par ticularlyi n
regionshav ing low st andards ofhy gi
ene and
poorsani tati
on,mayhav egr av ec onsequences
wi thr egardt ot hehi ghspr ead oft hisv irus.
Et hanoland di sinfectant s cont aining chl or i
ne
or bleachar eef fectiveagai nstcor onaviruses( 249-
252) . Appr opr i
ate pr ecaut i
ons need t o be
followed strictly
whil
ehandli
ngthest ool
sofpatientsinfect
ed wit
h
SARS-CoV-2.Bi owaste mat erial
sand sewage
fr
om hospitals must be adequat el
y
di
sinf
ected,t
reated,anddisposedofproperl
y.
The
si
gnif
icanceoffrequentandgoodhandhy gi
eneand
 Thel'
CStl
ll
so) thestt
it
ii
csi
'cl
aicdt
oSARS—OoX'2
viralloadsr eflectact i
vereplicat
ionoft hi
svir
usln
the upperr espi ratorytractand pr olonged vi
ral
sheddi ngaf tersy mpt omsdi sappear,i
ncludi
ngv i
a
stool.Thus,t hecur r
entcasedef i
niti
onneedst o
be updat ed al ong wi t
har eassessmentoft he
str
ategiest
obeadopt edforrestr
aini
ngtheSARS
-CoV-2outbreakspread(
245).Insomecases,t
he
vir
alloadstudiesofSARS-CoV-2hav eal
sobeen
usef ultor ecommend pr ecauti
onary measur es
whenhandl ingspeci fi
csampl es,e.
g.,feces.Ina
recentsur veyf om 17conf
r i
rmedcasesofSARS-
CoV- 2 infect
ion with
availabl
edat a(r
epresenti
ngdays0to13after
onset),
stoolsampl esf rom ninecases( 53%;day s0t o
11af t
eronset )wereposi ti
veonRT- PCRanal ysis.
Althought hev ir
alloadswer elowert hanthose
ofr espir
ator y
sampl es(r
ange,550copiespermlt
o
1.2110copiesperml),
thi
shasessenti
albiosaf
ety
impli
cati
ons(151).
The sampl es f r
om 18 SARS- CoV- 2-
positi
ve
pati
entsi
n Si ngapore who had t iavel
ed f r
om
Wuhant oSi ngaporeshowedt hepr esenceofv ir
al
RNAi nst oolandwhol ebloOdbut notinur i
neby
real
-t
imeRT- PCR( 255)
.Further,novelSARS- CoV-
2infect
ionshavebeendet
ectedl
navari
ety
of cl
i
nical
specimens,l
ikebr
onchoalveol
arl
avagefl
uid,
specifi
cquantit
ativeRT-rCRinthroatswaband
sputum sampl es col l
ected ffOl
R COVI D-
19-
i
nfectedindi
vi
duals.Theresult
sindi
catedthatthe
vir
alloadpeakedatar ound5t o6daysf ol
lowing
the onset of
sympt oms, andi trangedf rom104t o10copi es/ml
duringthi
stime( 151) .I
nanot herstudy ,
thev ir
all
oad
wasf oundt obehi gheri nthenasal swabst hant he
throat swabs obt ained f r
om COVI D-19
sympt omat i
c pat ients( S2).Al though i nit
ial
lyi t
wast houghtt hatv ir
all oadwoul dbeassoci ated
withpoorout comes,somecaser epor tshav e
shown
asympt omat icindi vidualswi t
hhighv i
ralloads( 247).
Recent l
y,thev iralloadi nnasalandt hroatswabs
of17sy mpt omat icpat ientswasdet er mined, and
higherv i
rall oadswer er ecordedsoonaf t
ert he
onset of sy mpt oms, particularlyin the
nosecompar edt ot het hroat.Thepat ternofv iral
nucleic acid sheddi ng ofSARS- CoV- 2-i
nfected
patientswassi mi l
art ot hatofi nf l
uenz apat i
ents
butseemedt obedi f
fer entfrom t hatofSARS-
CoV pat i
ent s. The viral
l
oaddet ectedi nasy mpt omat i
cpatientsr esembl edth
atofsy mpt omat icpat ient sasst udiedi nChi na,
which refl
ectst
he tr
ansmissi
on perspect
ive of
asymptomat i
c or sy i
ii
ptomati
c pat
ients
havingmini
mumsignsandsy
mpt oms(52).
Another
study,
SkAS-
Co\ -
2st
i‘
ai
nsav
ail
afahi
nt onal Ce
heNai
i nt
er
for Bi otechnol ogy I nformat ion and GI SAI D
dat abaseswer esubj ectedt omul tiple-sequence
ali
gnmentandphy l
ogenet i
canal ysesf orst udy i
ng
variat ionsi nt hev i
ralgenome( 260) .Al lthev i
ral
strai ns r evealed hi gh homol ogy of 99. 99%
(99. 91% t o100%)att henucl eotidel ev eland
99. 99%( 99.79%t o100'/ »)att heami noaci dl evel.
Ov eral lv ari
at i
onwasf oundt obel ow i nORF
regi ons,wi t
h13v ariationsi tesr ecogni zedi n
l
a,Ib,S,3a,M,8, andNr egions.Mut at i
onr at esof
30.53O/ o(29/ 95) and 29. 47% ( 28/ 95) wer e
obser v edatnt28144( ORF8)andnt 5782( ORFI a)
posi tions,r espect i
vely.Owi ng t osuch sel ect i
ve
mut at i
ons, af ewspeci ficregi onsofSARS- CoV- 2
shoul d not beconsider ed f ordesi gni ng pr imer s
and pr obes. The SARS- CoV- 2 r efer ence
sequence coul d pav e t he way t o st udy
mol ecul arbi ologyandpat hobi Ology ,alongwi th
dev el oping di agnost ics and appr opr i
ate
prev ent i
onandcont rolst r
at egiesf orcount er i
ng
SARS- CoV- 2( 260).
Nucl eicacidsofSARS- CoV- 2canbedet ected
from sampl es (64)such as br onchoal v eolar
l
av age fluid,sput um,
nasal
swabs,fi
berbronchoscopc br ush bi
opsy
speci
men,phar yngeal swabs,f eces,bl
ood,
andur
ine,
wit
hdif
ferentl
evel
sofdi
agnosti
c
DIAGNOSI
S OF SARS-
CoV-
2(COVI
D-
19)
RNAt estscanconf irmt hediagnosi sofSARS-
CoV- 2(COVI D-19)caseswi thr eal-ti
meRT- PCRor
next -generation sequenci ng ( 148,149,245,
246) . At pr esent , nucl eic aci d det ection
techni ques,l ike RT-PCR,ar e consi der
ed an
effect i
vemet hodf orconf ir
mi ngt hedi agnosisin
cli
nical cases of COVI D- 19 ( 148) . Sev eral
compani es acr oss t he wor l
d ar e cur rently
focusi ngondev elopingandmar keting SARS-
CoV- 2-
speci f
ic nucl eic aci d det ect i
on ki ts.
Mul tipl
elaboratoriesareal sodev elopi ngt hei
rownin
-houseRT- PCR.Oneoft hem i st heSARS- CoV-2
nucl eicaciddet ect i
onki tproducedbyShuoshi
Biot echnology ( doubl e f luor escence PCR
met hod) ( 150) . Upt o30Mar ch 2020, the
U.S. FoodandDr ug Admi ni
strat i
on ( FDA) had
grant ed 22 inv i
fro diagnost icsEmer gencyUse
Aut horizati
ons( EUAs) ,includingf ort heRT- PCR
diagnost i
cpanelf ort heuni versaldet ect
ionof
SARS- l
ike betacor onav iruses and
speci fi
cdetect i
onofSARS- CoV- 2,
dev el
opedbyt he
U.
S.CDC(
Tabl
el)
(25S,
259)
.
CoV—2( 329).
Similarly,the Nat i
onalVet eri
nary Ser v i
ces
Labor ator i
esof t
heUSDAhav er eport
edCOVI D-
19i nt i
ger sandl ionst hatexhi bit
edr espirat or y
signs l ike drycough and wheezi ng.The zoo
animal s ar e suspect edto havebeeni nfect ed
byanasy mpt omaticz ookeeper( 335).The t ot al
number of COVI D-19- posi ti
ve cases
i
nhumanbei ngsisincreasingatahi ghrate,ther eby
creatingi dealcondi ti
onsf orv iralspil
lovertoot her
speci es,suchaspigs.Theevidence obt ained f r
om
SARS- CoV suggest sthatpi gscan geti nf ect ed
with SARS-CoV- 2 (336) . Howev er,
exper iment ali
noculationwithSARS- CoV-2failedt o
i
nf ectpigs(329).
Furtherst udiesar erequi red toi dentifyt he
possi bleani malr eser voir
sofSARS- CoV- 2and
the
seasonal vari
ati
onintheci r
culationof t
hesev i
ruses
i
nt heani malpopul ation.Resear chcol l
abor ation
bet ween human and ani malheal t
h sect or si s
becomi nganecessi tyt oev aluateandi dent ify
the
possi bl
er i
skfact
orsoftransmissi onbetweenani mal s
andhumans.Suchcooper at
ionwil
lhelptodevi
se
eff
ici
entst
rategi
esfor
themanagementofemer
ging
zoonot
icdi
seases(12)
.
furtherst udi es( 332) .Rat hert han wai ting f or
fi
rmer ev idence on animal -t
o- human
transmi ssi on,necessar y prevent ivemeasur esar ead
vised,aswel l as f ollowi ng soci al di stanci ng
practicesamongcompani onani mal sofdi fferent
househol ds( 331) .Oneoft hel eadi ngv et erinar y
diagnost ic compani es,I DEXX,has conduct ed
l
ar ge-scal et estingf orCOVI D-19i nspeci mens
collectedf rom dogsandcat s.Howev er, noneof
thet estst ur nedoutt obeposi t
iv e(334) .
I
n a study conduct edt o
i
nv estigatet hepot ent i
alofdi f
fer entani malspeci cs
toactast hei ntermedi atehostofSARS- CoV- 2,it
was f ound t hatbot hf err
et s and cat s canbe
i
nf ectedviaex per i
ment alinocul ationoft hev ir
us.I n
addi t
ion,i nfect edcat sef fi
cient lyt r
ansi i
i
ittedt he
disease t o nai ve cat s( 329) .SARS-CoV- 2
i
nf ectionandsubsequentt r
ansmi ssioni nf erret s
wer ef oundt or ecapi tulatet hecl inicalaspect s
otCOVI D- 19 i n humans.The i nfect ed f erret s
alsoshedv i
rusv i
amul tipler out es, suchassal iva,
nasalwashes,f eces,and ur ine,post i
nf ect ion,
maki ngt hem ani dealani malmodelf orst udy i
ng
disease t ransmi ssion ( 337) . Exper iment al
i
nocul ationwasal sodonei not herani malspeci es
and f
ound t
hat t
he
dogshav
elowsuscept
ibi
l
ity
,whi
l
ethechi
ckens,
SARS—CoV—2.
Ther ei s a st eady i ncrease i nt he repor t
s
ofCOVI D-19i ncompani onandwi l
dani malsar ound
the wor ld.
Further studi es ar e r equiredto
ev aluatet he pot ential of ani mal s ( especially
compani on ani mal s)to serve as an
efficientreser voir
host t
hat can f urt
her al t
er t he
dy nami csofhuman- to- humant ransmi ssion( 330).
Todat e,t wopetdogs( HongKong)andf ourpet
cat s( oneeachf rontBel gium and HongKong,
twof rom t heUni tedSt ates)hav et estedposi ti
ve
forSARS- CoV- 2( 335) .TheWor ldOr ganizationfor
Ani mal Heal t
h ( OIE) has conf ir
med
thedi agnosi sofCOVI D-19i nbot hdogsandcat s due
to human- t
o-animal t ransmi ssion( 33l)
. The
simi lari
tyobser vedi nt hegenesequenceofSARS
-CoV- 2fromani nfectedpet owner andhi sdogf uuher
conf inns t he occur rence of human- to-animal
transmi ssion( 333).Event houghasy mpt omat ic,f
eli
ne speci es shoul d be consi dered a pot ential
transmi ssionr out efrontani i
iial
stohumans( 32fi)
.
Howev er, currently,ther ear enor epor t
sofSARS-
CoV- 2transmi ssionf rom f el
inestohumanbei ngs.
Basedont hecur rentev idence,wecanconcl ude
thatcat sar esuscept i
bl et oSARS- CoV- 2andcan
geti
nfect
edby
humanbei
ngs.
Howev
er,ev
idenceof
cat
-
(oneami noaci ddi ffer ence)t ot hatofSARS- CoV-
2.A compar i
son of t he genomes suggest s
recombi nat i
onbet weenpangol in-CoV- li
kev ir
uses
with t he bat -
CoV- RaTG13- l
ike v i
rus. Al lt hi
s
suggest st hepot entialofpangol i
nst oactast he
i
nt ermedi at ehostofSARS- CoV- 2( 145).
Human- wi ldlifei
nt eract i
ons, whi chare
increasi ngint hecont ext ofclir
natechange( 142) ,ar e
furtleTconsi der edhighr iskandr esponsi ble f orthe
emer gence of SARS- CoV. COVI D-19 i s al so
suspect edof hav i
ng asi mi larmodeof origin.Hence,
topr eventt heoccur renceofanot herz oonot i
c
spillover( l),exhaust ivecooi •dinat edef f ortsar e
neededt oi dent ify t
hehi gh-riskpat hogenshar bored
bywi ldani mal popul ations, conduct ingsur veill
ance
among t hepeopl e who ar e suscept ibl
e
tozoonot ic
spillover event s( 12),andt oimpr ovet hebiosecur i
ty
measur esassoci atedwi tht hewi l
dlif
et rade( 146) .
Theser ol ogi calsur v eil
lancest udiesconduct ed
i
npeopl el ivingi npr oximi tyt obatcav eshad
ear l
ieri dent i
fiedt hesei •
ologi ca1conf irmat i
on
ofSARS-r elat edCoVsi nhumans.Peopl eliv i
ng
att he wi l
dl i
fe- hulnan i nt erf
ace,mai nlyi nr ural
Chi na,ar er egul arly ex posed t o SARS- related
CoVs (
147)
.
Thesef
indi
ngswi
l
lnot
haveany
signi
fi
canceunt
il
a
montWul iani sar ecoi ii
bi nantv ii
'usott hebat
coronav irus and anot her cor onav i
rus of
unknownor igin.Ther ecombi nat i
onwasf ound
to hav e l iappened wi thin t he v iral spi ke
glycoprot ein, whi ch recogni zest he
cell
surfacer ccept or. Fur ther anal y sof t
si he
genomebasedoncodonusagei dent i
f i
edt he
snakeast hemostpr obabl eani malr eser voirof
SARS- CoV- 2( 143) .Cont raryt ot hesef indi ngs,
anothergenome anal y
si s pr oposed t hatt he
genome of SARS- CoV- 2i s9ó% i dent i
calt obat
coronav irus,r eflectingi tsor i
ginf rom bat s( 63).
The i nv olveinent of bat -derived mat er ialsi n
causingt hecur rentout breakcannotber ul edout .
Highr iski si nv olvedi nt hepr oduct ionofbat -
derivedmat er i
alsf orTCM pr act i
cesi nv olvi
ng
thehandl ingofwi ldbat s.Thei iseofbat sf or
TCM pr act i
ceswi llremai nasev erer i
skf ort he
occur r
enceofz oonot iccor onav ir
usepi demi csin
thefutur e( 139) .
Furthermor e,thepangol insar eanendanger ed
speciesofani mal st hathar borawi dev ar ietyof
vir
uses,i ncluding cor onav i
ruses ( 144) . The
coronav irus isolat ed from Mal ayan
pangol nsMani
i sj avani ca)showedav eryhi gh
ami
no aci
d i
dei
i
tit
y wi
thCOVI
D-
19àt
E(1OOOo)
,M(
98.
2%)
,N
(
96.
7%)
,andSgenes(
90.
4%)
.TheRBDof
Spr
otei
n
handl
i
ng of batsfor t
i'
adi
ng pur
poscs posCSd
consi
der
abl
er i
sk of t
ransmit
ti
ngz oonoti
cCoV
epidemi cs(139) .
Duet ot hepossi bl erol epl ay edbyf arm and
wild animal sinSARS- CoV-
2infect i
on,theWHO, i
nt hcir novel cor onavi rus
(COVI D-19)situat ionrepor t,
recommendedt heav oi danceof unpr ot ect edcont act
withbot hf ar m andwi l
dani mal s( 25) .Thel i
ve-
animalmar ket s,liket heonei nGuangdong,Chi na,
prov i
des a set ting f orani malcor onav ir
uses t o
ampl ifyandt obet ransmi ttedt onew host s,like
humans( 78) .Suchmar ketscanbeconsi der eda
criti
calpl ace f ort he or i
gi n ofnov elzoonot i
c
diseases and hav e enor mous publ ic heal th
signifi
cancei nt heev entof anout break.Bat sar e
the
reser voi
rsfor sev er alviruses;hence, ther oleof bat s
i
nt hepresent out breakcannot be r uledout( 140) .Ina
qual i
tati
v e st udy conduct ed f orev aluat i
ng t he
zoonot icriskf act orsamongr uralcommuni tiesof
sout hern Chi na, t he f r
equent human- ani mal
i
nt eractions al ong wi th t he l ow l evels of
env ir
onment albi osecur it
y wer ei dent i
fied as
signifi
cantr isksf ort heemer genceofzoonot i
c
di
seasei
nlocalcommuniti
es(141,
142).
Thecompr ehensi
vesequenceanal
ysi
sof
the
hav ingsev ereent eriti
sandbel ongst ot hegenus
Alphacor onav irus [ 106) . The out br eak was
associ atedwi thconsi der ablescal emor tal
ityof
piglets( 24,693 deat hs)acr oss f ourf ar r
ns in
Chi na
(l
34) .Thev i
rusi sol atedf romt hepi gletswasal most
i
dent i
calt oandhad95% genomi csiirilaritywi th
hor seshoebatRhi nol ophusspeci es)cor onav ir
us
HKU2, suggest ingabator i
ginof thepigv irus( 10ó,
134,135) .Iti sal soi mper ativet onot et hatt he
SADS- CoV out br eak st aued i n Guangdong
prov ince,neart hel ocat ionoft heSARSpandemi c
origin
(134) .Befor ethisout break, pigswer enotknownt o
be i nfected wi th bat -origin cor onav i
ruses.Thi s
i
ndi catest hatt hebat -ori
gincor onavi
r usj umped
to pi gby br caki ng t hespeci es bar r
ier .Thenext
stepoft hisj umpmi ghtnotendwel l
,si ncepi gs
are consi der edt hemi xing v essel f or inf l
uenza
Av i
ruses
duet otheirabili
t ytobei nfect edby bot hhuinanand
aviani nf l
uenz aAv i
ruses( l
3ó) .
Simi l
arly,theymayactast hemi xi ngv essel
for
cor onav i
ruses, sincet hey areinfrequent cont act with
both humans and i nulti
ple wi
ldli
fe speci
es.
Addit
ional
ly
,pi
gsar eal
sofoundtobesusceptibl
eto
i
nfecti
onwi thhumanSARS- CoVandMERS- CoV,
l
nakingthi
sscenar
ioanightmare(
109,137)
.l
ti
s
intactsev eral domest icandwi ldr uini nant s( 126) .
BoCoVi nf l
ictsneonat alcal f
di arrheai nadul tcat t
le,
l
eadi ngt obl oodydi arrhea( wi nt erdy sent er y
)and
respirator ydiseasecompl ex(shi ppi ngf ever )incat tl
e
ofal lagegr oups( 126) .BoCoV- l
ikev iruseshav e
beennot edi nhumans,suggest i
ngi tszoonot i
c
pot entialaswel l(127) .Fel i
neent ericandf el i
ne
i
nf ectiousper it
oniti
s( FIP)vi rusesar et het wo maj or
feli
neCoVs( 12b),wher ef elineCoVscanaf fect
the
gast rointest inaltr
act ,
abdomi nal cav ity(per i
tonitis),
respirat oryt ract,andcent ral ner v oussy stem ( l28).
Cani nesar eal soaf fect edbyCoVst hatf allunder
different gener a,namel y,canineent er iccor onav i
rus
n Al
i phacor onav irt
fs and cani ne r espiratory
cor onav irusinBet acor onnv i
ru.s, aff ect ingt heent eric
andr espi rator yt r
act ,respect ivel y( 129,130) .I BV,
under GammacOl “OnaVi l
his,causes di seases of
respirat ory ,
urinary,andr epr oduct ivesy st ems, wi th
subst ant ialeconomi cl osses i n chi ckens ( 13I,
132) .Insmal llabor atoryani mal s, mousehepat i
ti
s
vir
us,r atsi alodacr y oadeni tis cor onav ir
us,and
guineapi gandr abbi tGor onav i
rusesar et hemaj or
CoVs associ ated
withdi seasemani fest ati
onsl ikeent critis,
hepati
ti
s,andr
espir
ator
yinf
ect
ions(
l0,
133).
Swineacut
ediarr
heasyndr
omecoronav
irus
î
), 124,127} .
Coi 'oii
ai i
ius i nl?ctioiiisl i
iikcd t e›
diff
erent kindsof clinical mani festations,var yingfrom
enteriti
si n cows and pi gs,upperr espi r
at or y
diseasei nchickens, andf at al
respi ratoryinfect ionsi n
humans( 30) .
Amongt heCoVgener Al
a, ›
lincor onav i
ru. sand
Betat'oionuv i
ruy ’ i nf ect i nammal s, whi le
Gummacor onav i
i•us and Del tacor onuv irus
mai nly inf ectbir
ds, fi
shes, and,
somet i
i
nes, mammal s( 27,29,l Ofa).Sev eralnov el
coronav iruses t hat come under t he genus
Deltacoi onuv i
ru.s hav e been di scov ered i nt he
pastf rom bi rds,l i
keWi geoncor onavirusHKU20,
Bulbul coronav i
rus HKU11, Muni a
coronav irusHKU13, whi te-eye cor onav irus
HKU16, ni ght-her oncor onav irusHKU19, and
coinmonmoor hencor onav irusHKU2I ,aswel las
fi
oinpi gs( por cinecor onav irusHKU15)( fi
,29) .
Transmi ssible gast roent er i
tis v i
rus ( TGEV) ,
porcine epi demi c di ar rhea v i
rus ( PEDV) ,and
porcine hei raggl ut inat ing encephal oiny eli
tÎS
VÎFUS (PHEV)
aresomeof t
hecor onav irusesof swi ne.Amongt hem,
TGEV and PEDV ar er esponsi blcf orcausi ng
severe gast roent er i
tis i n y oung pi glet s
withnot ewor thy mor bi di
ty and i nor tality.
Inf
ecti
onwi thPHEValsocausesenter
ici
nfect
ion
but can cause
encephal
i
tisduet
oit
sabi
li
tyt
oinf
ect
thener
vous
chronicdi seases,espcci all
yhi ghbl oodpr essul e
anddi abetes,wer ef oundt obemor esuscept ible
to r espiratory f ai l
ur e and, t herefore, had
poorerprognoses.Pr ov i
dingr espirator ysuppor tat
early stages i mpr ov ed t he di sease pr ognosi s
andf acili
tatedr ecov er y(1S) .TheARDSi nCOVI D-
19i sduet ot heoccur renceofcy tokinest or ms
thatr esultsi n exagger ated i mmune r esponse,
i
mmune regulat or y
networ ki
mbal ance,and, fi
nally,
mul t
iple-organfailur e
(122). I n addi tion t o t he exagger at ed
i
nf l
ammat oryresponse seen i n pat ient s
withCOVI D-19pneumoni a,thebi leductepi thel ial
cell
- der i
ved hepat ocytes upr egulatc ACE2
expression i n l i
ver t issue by compensat or y
proli
ferati
on t hatmi ghtr esul tin hepat ict i
ssue
i
njury( 123).

CORONAVI
RUSESI
NANI
MALSAND
ZOONOTI
CLINKS ABRIEF
VI
EWPOINT
Coronav
iruscancausedi seaseinsever al
speciesofdomes t
icandwildanimals,aswel l
ashumans( 23)
.Thediff
erentanimalspecies
thatar einfect
ed wit
h CoV i ncl
ude hor
ses,
camels,cat
tl
e,swine,dogs,cat
s,r
odent
s,bi
rds,
fer
ret
s, minks, bat
s, r
abbi
ts,
snakes,
andvari
ousotherwi
ldani
mals(
20,
30,
79,
t
her
c 11i
t t
ivci
i en11cet
'
tiI
cc‹
t1f
luI
u it
ic i1li aci c›
1
SARS- CoV- 2/ COVI D-19onpi '
egnancy .Researcher s
hav e ment ioned t he pr obabi li
ty of i n « km
transmi ssion ofnov elSARS- CoV- 2
fromCOVI D-I 9-i
nf ectedmot her’sto
theirneonat esi nChi nabased
upont her i
sei nlgMandl gGant ibody levelsand
cy t
okinev aluesi nthebl oodobt ainedf romnewbor n
i
nf ants i mmedi ately post birth;howev er, RT-
PCRf ailed t o conf ir
m thepr esence
of SARS- CoV- 2
genet icmat er i
alinthei nfants(2S3) .Recent studiess
howt hat atleast insomecases, pr etenddel iver
y
andi t
sconsequencesar eassoci at edwi t
ht hevi
rus. N
onet hel ess,somecaseshav eraiseddoubt sforthe
l
ikel i
hoodof ver ti
cal transmi ssi on( 240—243) .
COVI D-19 i nfection was associ ated wi th
pneumoni a, and some dev eloped acut e
respirat orydi stresssy ndr ome( ARDS) .Thebl ood
biochemi stryi ndex es,suchasal bumi n,lact ate
dehy dr ogenase,C-r eact i
v epr otein,l ymphocy tes
(percent ),andneut rophils( percent )gi veani dea
aboutt hedi seasesev er
ityinUOVI D- 19i nf
ect ion
(121) .Dur ingCOVI D-19,pat i
ent s may pr esent
l
eukocy tosis, leukopeni a wi th
l
y rnphopeni a ( 244) ,hy poal bumi nemi a,andan
i
ncrease of l act
ate dehydrogenase,aspartate
tr
ansaininase, al
anine
aminotransfer
ase,
bil
ir
ubin,
and,especi
all
y,
D-di
mer
resulting insev erei ntersti
t i
ali nflammat ionof
the l ungs. Thi s i sevident on comput ed
tomogr aphy ( CT) i mages as gr ound- gl ass
opaci tyint hel ungs.Thi slesioni ni
tiall
yinvolv esa
singlelobebutl aterexpandst omul t
iplelungl obes
(11S) .The hi stologi calassessment of l ung
biopsy sampl es obt ained f rom COVI D- 19-
i
nf ected pat ients r ev eal
ed di ff
use al veol ar
damage,cel l
ularf ibi omy xoid exudat cs,hy al inc
membr ane f or mat i
on, and desquamat i
on of
pneumocy tes, indi cative of acut e
respiratorydistresssy ndr ome( l 19) .
Itwasal so
found t hatt he SARS- CoV- 2-i
nf ected pat ient s
often hav el ymphocy t
openi a wi t
h or wi thout
l
eukocy te abnor mal iti
es. The degr ee of
l
y mphocy topeni a gi ves an i dea aboutdi sease
prognosi s, as i t i s f ound t o be
posi t
ivelycorrelatedwi th disease sev eri
ty( 11S) .
Pregnantwomenar econsi der edt ohav eahi gher
ri
sk of get t
ing i nf ect ed by COVI D-19. The
cor onav i
rusescancauseadv erseout comesf or
thef etus,suchasi nt rauteri
negr owt hr estri
ct ion,
spont aneous abor tion,
pretermdel ivery,
andper inataldeath.
Nev ert
heless,t he possi bil
it
y of i ntrauter ine
maternal
-f
etal t
ransmissi
on (ver
ti
cal
tr
ansmissi
on)ofCoVsi slow andwasnotseen
duri
ng ei
ther
theSARS-
orMERS-
CoVoutbr
eak(120)
.However,
wi l
dani mal st ohumansdur ingSARSandMKRS
out breaks( 79,102) .Thepossi bilityofcr ossi ng
the speci esbar ri
erf ort het hirdt i
mehasal so
been suspect ed i nt he case of SARS- CoV- 2
(COVI D-19) .Bat s ar er ecogni zedas a possi ble
nat uralr eservoirhostofbot hSARS- CoVandMERS-
CoVi nf ection.I
ncont r
ast ,t
hepossi bleintermedi aryh
ost i
st hepal m ci v
et f or SARS- CoV and t he
droni edar ycamelf orMERS- CoVi nfection( 102) .
Bat sar econsi deredt heancest ralhost sforbot h
SARSandMERS( 103) .Bat sar eal soconsi der ed
ther eser voirhostofhumancor onav i
rusesl i
ke
HCoV- 229EandHCoV- NL63( 104) .I nthccaseof
COVI D-19,t herear et wopossi bili
tiesf orpr imar y
transmi ssion:itcanbet r
ansmi tt
edei therthr ough
i
nt ermedi atehost s,si mi lartot hatofSARSand
MERS, or di r
ect ly f r
om bat s ( 103). The
emer gencepar adigm putf or war di nt heSARS
out break suggest st hat SARS- CoV or iginat ed
from bat s( r
eser voirhost )andl at erjumpedt o
civets (intermedi ate host )
andi ncor poratedchangeswi t nt
hi he r
ecept or-
bindi ngdomai n(RBD)t oi mpr ovebi ndingt oci vet
ACE2. Thi s civet-adapt ed v i
rus, dur i
ng t heir
subsequentex posur et ohumansatl ivemar ket s,
promoted f
urt
her adapt
ati
ons t
hat
resul
tedi
ntheepi
demicst
rai
n(104)
.Tr
ansmi
ssi
on
canal
so
evaluat etheprogr essi onof i
nf ect ion( 29l).I
n
addit i
ont oal loft heabov ef indi ngs,sequenci ng
and phy logenet ics ar ecr it
ical i nthecor rect
ident ifi
cat i
onandconf i
rmat ionoft hecausat ive
vir
al agent and
usef ultoestablishrel at i
onshi pswi t
hpr ev i
ousisol ate
sandsequences,aswel last oknow,especi all
y
during an epi demi c,t he nucl eot i
de and ami no
acid mut at i
ons and t he mol ecul ardi vergence.
The r apid dev elopmentand i mpl ement ation of
diagnost ic t
est s
against emer gingnov eldiseasesl i
keCOVI D-19pose
significant chal lenges due t o t he l ack of
resour cesandl ogist icallimit ationsassoci atedwi tha
nout break( 155).
SARS- CoV- 2i nf ect i
oncanal sobeconf ir
med
by isol ation and cul t
ui'i
ng.Thehuman ai rway
epithel i
al
cell
cul turewasf oundt obeusef ulinisol ating SARS-
CoV- 2( 3).
Theef fi
ci ent cont rol ofan outbreak
dependsont her api ddi agnosi soft hedisease.
Recent ly
,i nresponset ot heCOVI D- 19out break,
1-stepquant itati
v er eal -
timer ev erset ranscr i
ption-
PCR assay s wer e dev eloped t hatdet ectt he
ORFl bandN r egionsoft heSARS- CoV- 2genome
(156).Thatassaywasfoundtoachiev
ether api
d
detecti
on of SARS-CoV-
2.Nucl ei
c acid-
based
assaysoff
erhi
ghaccur
acyi
nthedi
agnosi
sofSARS-
cl
ini
caltr
ial
swi llnotbeavail
able.Thenewly
devel
opeddrugscannotbemar
ketedduet
othel
a
ckofendusers.

Vacci
nes
TheSpr oteinpl aysasi gni ficantr ol
ei nt he
i
nduct i
onof pr otectivei mmuni ty agai nst SARS-
CoV by medi ati
ng T- cell r esponses and
neutralizingant ibodypr oduct ion( 16S) .Inthepast
few decades,
wehav eseensev eralat
tempt stodev elopav acci ne
againsthumancor onav i
rusesbyusi ngSpr otein
ast het arget( 165,169) .Howcv er ,thedev eloped
vaccineshav emi ni
malappl icat ion,ev enamong
closelyr elat edst r
ainsoft hev irus, duet oal ackof
cross-pr otect i
on.Thati smai nlybecauseoft he
extensi vedi v ersityexistingamongt hedi ff
er ent
antigeni c v ar i
ant s of t he v irus ( 104) . The
cont r
ibut i
onsoft hest ructuralpr ot ei
ns,l i
kespi ke
(S), mat ri
x ( M) , smal l env elope ( E) , and
nucleocapsi d( N) pr oteins,of SARS- CoV t o
i
nducepr ot ectiv eimmuni tyhasbeenev aluat ed
by expr essi ng t hem i n a r ecombi nant
parainfluenza v irust ype3 v ect or( BHPI V3) .Of
oteinswi thout thepresenceof Spr ot einwoul dnot
note, t
he
resul
twasconcl
usi
vet
hat
theexpr
essi
onof
M,E,
orN
›
icci
i
icI
i)
i’
Ct)
¥ID-
li
i
il
°:
ii
’
til
ti
lel
miui
tht
he Vacci
ne
Resear chCent er( VRC)oft heNat ionalI nsti
tut eof
AllergyandI nfect iousDi seases( NI AID),par tof
the Nat ionalI nst i
tut es ofHeal th( NI H)( l52) .
By empl oy i
ngmRNAv acci nepl atfor mt echnol ogy ,
av acci necandi dat eexpr essi ngSARS- CoV- 2spi ke
prot eini sl ikel yt ogot hr oughcl ini calt estingi n
the coi ni ng mont hs( 1b0) .On 16 Mar ch 2020,
Jenni fer Hal lerbecame t he f irst per sonout side
Chi nato r ecei v e an exper i
ment al v acci ne,
dev eloped by
Modcr na, agai nst thispandemi cv i
rus. Modema,
alongwi t hChi na'sCanSi noBi ologi cs,became
thef i
rstr esear chgr oupt ol aunchsmal lcli
ni cal
tri
als of v acci nesagai nstCOVI D-19. Theirstudy i
s
eval uating t he v acci ne's saf ety and abi l
i
tyt o
tri
ggeri mmuner esponses( 296).
Scient istsf romal lov erthewor ldar et ryi
nghar d
to dev elop wor ki ng v acci nes wi th r obust
prot ectivei mmuni tyagai nstCOVI D- 19.Vacci ne
candi dat es,likemRNA- 1273SARS- CoV- 2v acci ne,
INO- 4800 DNA cor onav i
rus v acci ne, and
adenov irust y pe5v ect orv acci necandi dat e( Ad5-
nCoV) ,ar eaf ew exampl esunderphaseIcl i
ni cal
tri
als, whi le sel f
-
aicpl i
fyingRNAv acci ne, oralrecombi nant COVI D-
19vacci
ne,
BNT162,pl
ant-
basedCOVID-
19
vacci
ne.
andIi
-Key
pepti
deCOVID-19v
acci
near
e
›accinci nBALB/ ci ii
iccwasl oundl oi nducel ong-
l
ast i
ngneut ral i
zingi mmuni tyagai nstMERSspi ke
pseudot ypedv i
rus,char acter izedbyt hei nduct i
on
ofsy stemi cI gG,secr etoryl gA,andl ung- resident
memor y T-cel l responses (
177) .
Immunoi nfor mat ics met hods hav e been
empl oy ed f or t he genome- wide scr eeni ng of
potent ialv acci ne t arget s among t he di f
ferent
i
mmunogensofMERS- CoV( 175).TheN pr ot ein
andt hepot ent i
alB- cellepi t
opesofMERS-CoVE
protei n hav e been suggest ed as
i
ininunopr ot ectivet ar getsi nducing bot h T- cell
andneut rali
zi ngant ibodyr esponses( 17S, 179) .
Thecol labor ativ eeffortofther esearcher sof
Rocky Mount ain Labor at ories and Oxf or d
Univer sityisdesi gningachi mpanz eeadenov i
rus
-vector ed v acci net o count erCOVI D-19( 150) .The
Coal iti
onf orEpi demi cPr epar ednessI nnov ations
(CEPI )hasi nit
iat edt hreepr ogramst odesi gn
SARS- CoV- 2 vacci nes ( 1S1) . CEPI has a
coll
abor ative proj ect wi th
Inoviofor desi gningaMERS- CoVDNAv acci nethat
couldpot entiat e ef f
ect i
veimmuni ty
.CEPI andt he
Univ ersity of Queensl and ar e desi gning a
mol ecul arcl amp v acci ne pl atf
orm f orMERS-
CoVandot
her
pat
hogens,
whi
chcoul
dassi
sti
ntheea
si
er
i
f
den'
.
.E nhf ‘
fendedy«hde’
tu e Da
histocompat ibil
ity compl ex cl ass Imol ecul es.
Theypot ent iallyinducei mmuner esponses( 176) .
Ther ecombi nantv acci necan bedesi gned by
usingr abiesv irus( RV)asav iralv ect or.RVcan
bemadet oexpr essMERS- CoVS1pr oteinoni ts
surfacesot hat ani mmuner esponsei si nduced
againstMERS- CoV.TheRVv ect or-basedv acci nes
against MERS- CoVcan i nduce f ast er ant i
body
responseaswel lashi gherdegr eesofcel lular
i
mmuni ty than the Gi •ain-posi tive
enhancer mat ri
x(GEM) particlev ector-basedv acci ne.
Howev er,t he l attercan i nduce a v ery hi gh
antibodyr esponseatl owerdoses( 167) .Hence,
the degr ee ofhumor aland cel lulari mmune
responsespr oducedbysuchv acci nesdepends
upont hev ect orused.
Dual v
acci neshav ebeenget tinglnOl epopul ar
recently. Among t hei r
,t he r abi es v i
r us-
basedv ector edv acci nepl atfonni susedt odev elop
vaccinesagai nstemer ging i nfectiousdi seases.
Thedualv acci ne dev eloped f rom i nact ivated
rabies v i
rus par ti
clest hat expr esst heMERS-
CoVSl domai nof S pr otein was f ound t oi nduce
i
mmuner esponsesf orbot hMERS- CoVandr abi es
vir
us.The v acci nat ed mi ce wer ef ound t o be
compl
etel
yprotect
edfrom chal
l
engewi
thMERS-
CoV(
169).
Thei
ntr
anasal
SARS- CoV and SARS- li
ke ( SL) CoVs t o
ev aluat et he possi bil
it
y of
rcpur posedv accinesagai nst COVI D- 19. Thi s
st rategy wi l
lbe hel pfuli nt he scenar ioofan
out br eak, sincemucht imecanbesav ed,because
pr eliminar yev aluation,i ncl udingt ov i
trost udies,
already woul d be compl eted f orsuch v accine
candi dat es.
Mul ti
epi topesubuni t
vacci nescanbeconsi dered
a pr omi sing pr event iv
e st rategy agai nst t he
ongoi ng COVI D-19 pandemi c. / i7 silico aRd
adv anced i mr nunoinf orniat ict ool scanbeused
to dev elop mul tiepit
ope subuni tv accines.The
vacci nest hatar eengi neer ed byt hi
st echni que
can be further ev aluated
usi ngdocki ngstudiesand, iffoundef fective,thencan
be f urtherev aluated i n ani malmodel s( 365) .
Ident i
fyingepi topest hathav et hepot enti
altobecome
a v accinecandi dateis cr i
tical t
o dev eloping an
ef fect i
ve v accine agai nst COVI D- 19. The
i
r nirunoi nf ormat i
csappr oachhasbeenusedf or
i
ecogni zing essent i
alepi t
opes of cy totoxicT
l
y mphocy tesandBcel l
sfromt hesur face
gly copr ot ein of SARS- CoV- 2. Recent ly, a
fewepi topeshav ebeenr ecogni zedf romt heSARS-
CoV-
2surf
acegl
ycoprot
ein.
Theselectedepi
topesexpl
ore
dtar
geti
ngmolecul
ardynamicsimulati
ons,
willhel pt oi dentifypotent ialS pr otei nv accine
candi datesi nSARS- CoV- 2.Ther efor e,v accine
strategi es based on t he whol e S pr otein,S
prot einsubuni t
s, orspecificpot ent ialepi topesof
Spr ot einappeart obet hemostpr omi singv accine
candi dat es agai nstcor onav i
ruses. The RBD of
theS1subuni t of S pr otein has a super i
or
capaci tyt oi nduceneut ralizingant i
bodi es.Thi s
proper tyoft heRBDcanbeut i
li
zedf ordesi gning
pot ent i
alSARS- CoV v acci nes ei therbyusi ng
RBD- cont aining r ecombi nant pr ot ei
ns or
recombi nantv ectorst hat enc ode RBD ( 175) .
Hence, the super ior genet i
c
simi larityexistingbet weenSARS- CoV- 2andSARS-
CoVcanbeut ili
zedt or epur posev acci nest hat
hav epr oveni iiv i
troeffi
cacyagai nstSARS- CoVt o
be ut i
li
zedf orSARS- CoV- 2.Thepossi bili
tyof
cross-pr otect ion in COVI D-19 was ev aluated
bycompar i
ngt heSpr oteinsequencesofSARS-
CoV- 2wi tht hatofSARS- CoV.Thecompar ati
ve
anal ysisconf irmed t hatt he v ar i
abl er esidues
wer ef oundconcent r
atedont heS1subuni tofS
protei n,ani mpor t
antv accinet ar getoft hev i
rus
(150) .Hence,t he possi bil
ity of SARS- CoV-
speci f i
cneut ralizi
ngant ibodi espr ov idingcr oss-
pr
otecti
on t
o COVID-19
might
belower
.Funher
geneti
canal
ysi
sisr
equi
red
taeempl oy edt o‘SARS- CoV- 2-i
ii
t“ectedpat ient s.
Thesepossessbenef itsofeasyaccessi bili
tyand
recogni zed phar macoki net i
c and
phar macody nami cact iviti
es,st abili
ty,doses,and
side ef fect s( 9).Repur poseddr ugs hav e been
studi ed f or t reatingCoV i nfections, l ike
l
opi nav ir/ri
tonav ir,andi nterf
er on-1§ r ev ealed i fl
vitr
o ant i-MERS- CoV act ion. The i a v ivo
exper imentcar riedouti nthei i
onhumanpr imat e
model of common mar moset st reat ed wi th
l
opi nav ir/ri
tonav irand i nterferon bet a showed
super iorpr ot ectiveresul tsint reatedani mal st han
i
nt heunt reat edones( 190) .A combi nationof
thesedr ugsi sbei ngev aluatedt ot reatMERSi n
humans( MI RACLEt ri
al)( 191).Theset wopr otcase
i
nhi bitors( lopi nav i
randr i
tonav ir),
i
ncombi nationwi th
ri
bav i
rin,gav eencour agingcl i
nicalout comesi n
SARS pat ient s, suggest i
ng t heirt herapeut ic
values( 165) .Howev er,i nt hecur rentscenar io,
due t ot hel ack ofspeci fi
ct her apeut ic agent s
agai nst SARS- CoV-
2,hospi talizedpat ientsconf ir
medf or t
he di sease
aregi ven suppor tivecar e,likeoxy genandf luid
therapy , al ong wi th ant ibiotic t her apy f or
managi ngsecondar ybact eriali nfect i
ons( 192) .
Pati
ent
s wit
h novelcoronavi
rus or COVID-
19
pneumoni
awhoar
emechanical
l
yvent
il
atedof
ten
 \
iuondt
hec dr
i:
ii
cc1c‹
›i
up‹
›t
inet
s.4- ›
cIopcui
-
l-en-3-yl
ai nino)-5-[
2-(4-
iodopheny l)hydraziny l
j-
4H- 1,
2,4-triazole-
3-thioland
4-(cyclopent -
l-en-3-ylami no)-5-[
2- (4-
chloropheny l)
hy draziny1]-4H-1,2,4-tr
iazole-
3-thiol
wer efoundt obet hemost potent .
Thesecompounds
wer e usedf ori i
isi /i
ce st udi es,and
mol eculardocki ng wasaccompl i
shed i nto
theactivebi ndingsi teof MERS- CoV
l
ielicasensp13 ( 21) . Furtherst udies
arerequir ed forev al
uat i
ngt het herapeutic
potentialoft hesenewl yidentif
iedcompoundsi nthe
management ofCOVI D-19infect i
on.

Passi
veI
mmuni
zat
ion/
Ant
ibody
Ther
apy
/MAb
Monocl onal antibodi es(MAbs)maybehel pful
int
he
intervention of di sease in CoV-
exposed
i
ndividuals.Patientsrecover ingfromSARSshowed
r
obustneut r
alizing ant ibodi esagai nst thisCoV
inf
ection( 164) .AsetofMAbsai medat theMERS-
CoV S pr otein-speci ficdomai ns,compr isi
ng
sixspeci fi
cepi t
opegr oupsi nter
actingwi t
h
receptor-binding, membr ane f usion,andsial
ic
aci
d- binding
sit
es,makeupcr ucialentrytasksof Sprotei
n(198,
199).Passi
vei
mmunizat
ionemployi
ng weaker
and
st
rongly neut r
ali
zi
ng ant i
bodies provi
ded
consider
abl
eprot
ecti
onin miceagainstaMERS-
admi nister ingt heappr oveddose( 340) .Howev er,
i
v ermect in,bei ngahost -
dir ectedagent ,ex hibits
ant i
v i
ralact i
v i
ty by t argeting a cr iti
calcel lular
processoft hemammal i
ancel l
.Ther ef ore,t he
admi nistrat ion of i v ermect i
n,ev en at l ower
doses,
willreducet hev irall
oadat ami nor level.Thi ssl i
ght
decr easewi llpr ovideagr eatadv ant aget ot he
i
mmunesy st emf ormount ingal ar ge-scal eant iviral
responseagai nstSARS- CoV- 2( 341) .Fuuher ,a
combi nat i
on of iver mect in and
hy droxy chl oroqui ne mi ght hav e a sy ner gistic
effect , since i
v ermect io
reducesvi ralreplication, whi l
ehy dr oxychl oroqui ne
i
nhi bits t heent ryof thev i
rus i nt hehost cell(339) .
Fur ther,i i
iv ivo st udi esandr andomi zedcl inical
cont r
olt rials ar er equi red t o under stand t he
mechani sm aswel last hecl inicalut il
ityoft his
promi singdr ug.
Naf ainost atisapot enti nhi bitorofMERS- CoV
that act s by pr ev ent ing membr ane f usion.
Nev ertheless, i
tdoesnot hav eany sortof inhi bit
or y
act i
on agai nst SARS- CoV- 2 i nfect i
on ( 194) .
Recent ly, sev eral newl y sy nt hesi zed
hal ogenat edt ri
azol ecompoundswer eev aluat ed,
using f
luorescence r
esonance ener
gy transf
er
(FRET)-
basedheli
caseassays,
for
thei
rabi
l
ity
toi
nhi
bit
in anot hCf case st udy ,t he aut hor s r aised
conccmsov ert heef ficacyofhy dr oxy chl oroqui ne-
azitli
roiny cini nt het reat ment ofCOVI D-19pat ient s,
sincenoobser v ableef f ectwasseenwhent hey wer e
used. Insomecases, thet reatment
wasdi scont nuedduet
i ot hepr olongat i
onoft he
QT int er val (307) .
Hence, fuuher randomi zedcl i
ni caltrialsar erequi red
bef oreconcl udingthi smat ter.
Recent ly,
anot her FDA- appr oveddr ug,
i
v ermect in,was r epor t ed t oi nhi bitt he i i
iv i
tro
repl i
cat ion ofSARS- CoV- 2.The f indi ngs f r om
thisst udy indicat ethatasi nglet reat ment oft hi
sdr ug
wasabl et oi nducean- 5, 000- foldr educt i
oni nt he
viralRNAat48hi ncel lcul tur e.( 305) .Oneoft he
mai ndi sadv ant agest hatl i
mi tt hecl inicalut il
ityof
i
v ermect i
ni si tspot ent i
alt ocausecy totox i
ci ty.
Howev er ,al tering t he v ehi cles used i nt he
formul ations,thephar macoki net icpr oper ti
escanbe
modi f
ied, thereby havi ngsi gnificant cont rol over t he
syst emi c concent rat ion of i ver mect in ( 33S) .
Based
ont hephar inacoki net icsi mul ation,itwasal sof ound
that i
ver mect i
nmay hav elimi tedt her apeut i
cutili
tyi n
managi ng COVI D-19, si nce t he i nhibitory
concentr
ati
on that has t
o be achi
eved for
eff
ecti
ve ant
i-
SARS-CoV-
2acti
vit
yisf
arhi
gher
thant
he
humans.Thebr oad- spcct ruinact ivi
tyexhi bi
tedby
remdesi vir
wi ll
hel pcont rolthespr eadof diseasei n
theeventofanewcor onav i
rusout break.
Chloroqui nei sanant imal arialdr ugknownt o
possess ant iviralact i
vity duet oits abi l
ityt o
blockvi rus-cellf usionbyr aisi
ngt heendosomal
pH necessar yf orf usi on.I tal so i nterfereswi th
vius-r
r ecept orbi ndi ng byi nter f
er ing wi tht he
terminal gl y cosy l
at i
on of SARS- CoV cel lular
receptors, suchasACE2( 196) . I
nai•ecent
mul ti
center cl inicalt ri
al t hat was conduct ed
i
nChi na,
chlor oqui ne phosphat e was f ound t o
exhibit bot h ef ficacy and saf ety i n t he
therapeut i
cmanagement ofSARS- CoV- 2-
associatedpneumoni a( 197) .Thi sdr ugisal ready
i
ncludedi nt het reatmentgui delinesi ssuedbyt he
NationalHeal th Commi ssi on oft he Peopl e's
Republ i
C ofChi na.Thepr eliminar ycl i
nicalt r
ials
usingliydroxy chloroqui ne,anot herami noqui noli
ne
drug,gav e pr omi sing r esul t
s.The COVI D-19
patientsr ccci ved 600mg ofhy droxy chloroquine
dail
y along wi th az i
t hroiiiycin as a si ngle-arm
protocol. Thi s pr otocol was f ound t o be
associatedwi tha not ewor thyr educt i
oni nv i
ral
l
oad. Fi nally,i tr esul tedinacompl et e cur e(271);
however,
thest
udy
comprisedasmal
lpopul
ati
onand,
hence,
the
act i
v ity agai nst MERS,War bur g,Ebol a,and
Chi kunguny av i
ruses( 306) .Ev en t hough i thad
broad- spect rum act i
vity,itwasnegl ect edf oran
extendedper iod.Ti loronei sanot herant ivir
aldr ug
that mi ghthav eact ivi
tyagai nst SARS- CoV- 2.
Remdesi vir,anov elnucl eot i
deanal ogpr odr ug,
wasdev el
opedf ort reat ingEbol av ir
usdi sease
(EVD) ,and i twas al so f ound t oi nhibitt he
repl i
cat i
on of SARS- CoV and MERS- CoV
i
npr imar yhumanai rway epithel i
alcel l
cul t
ur esystems
(195) .Recent l
y,i nv i
tro st udyhas pr ov en t hat
remdesi vir
hasbet terantiv i
ralact i
vitythanl opinav ir
andr itonav ir.Further ,inv i
vost udiesconduct edi n
miceal soi dent i
fi
edt hatt reat mentwi thr eindesi vir
i
mpr ov edpul monar yf unct ionandr educedv i
r al
l
oadsandl ungpat hologybot hinpr ophy l
acticand
ther apeut i
c regi mens compar ed to
l
opi nav ir/r
itonav i
r -
IFN- yt r
eat menti nMERS- CoV
i
nf ect ion( S).Remdesi v i
ral soi nhibitsadi ver se
rangeof coronav iruses, i
ncl udi ngci r
cul atinghuman
CoV, zoonot icbatCoV, andpr epandemi czoonot ic
CoV( l95) .Remdesi ViFİ Sal soconsi der edt heonl y
ther apeut i
c dr ug t hat si gnificant l
y r educcs
pulmonar ypat hology (8).Allthesef i
ndi ngsi ndicate
that remdesi virhast obef urther evaluat edfor it
s
chlor oqui ne,test edi ii
coi npai i
sont orei rdesivirand
favipiravir(
broad- spect rumant ivir
aldrugs) reveal ed
reindesi virandchl oroqui net obehi ghlyef fect ive
agai nst SARS- CoV- 2 i nf ect i
on i iiv itr
o ( 194) .
Ribav i
rin,penci cl ov i
r,and f avi
pi r
av irmi ghtnot
possessnot ewor thyi iv
i iv o antiviralact ionsf or
SARS- CoV- 2,si ncehi gherconcent r
at ionsoft hese
nucl eosi deanal ogsar eneededi nvitr
ot olessen t he
vir
ali nfection.Bot hr emdcsi v
irand chl oroqui ne
arebei ngusedi nhumanst ot r
eatot herdi seases,
and such saf er dr ugs can be expl or ed f or
assessi ngt heiref f ectiv enessi nCOVI D-19pat ient s.
Sev eral t her apeut ic agent s, such as
l
opi nav ir/
rit
onav ir, chloroqui ne, and
l
iydr oxy cli
loroqui ne,hav ebeenpr oposedf ort he
cli
ni cal management of COVI D- 19 ( 299) .A
mol ecul ardocki ngst udy ,conduct edi nt heRNA-
dependentRNApol ymer ase( RdRp)ofSARS- CoV-
2usi ng di fferent commer cial
ly av ailable
ant i
pol yrnerasedr ugs, ident if
ied t hat drugssuchas
ri
bav ir
in,r emdesi v ir
,gal idesi vir
,t enof ovir,and
sof osbuv i
rbi ndRdRpt ight ly,indicat ingt hei rv ast
Fotent ialtobeusedagai nst COVI D-19( 305) .
A
broad- spect rumant ivi
ral drugt hat wasdevel opedi n
theUni tedStat es,til
or onedi hy drochloride( t
il
orone) ,
i
njur yassoci atedwi thhui i
ian-
machi neincoor dinat i
on ( 122) . The r esult
obtai ned f
rom a
cli
nical studyof fourpatient si
nf ectedwithCOVI D-
19 cl aimed t hat combi nat ion therapy usi ng
l
opi nav ir
/ri
tonav i
r, ar bidol, and Shuf eng
Jieducapsul es( traditi
onalChi nesemedi ci
ne)was
found t o be ef fect i
veinmanagi ng COVI D-
19pneumoni a(193) .Iti sdi f
ficulttoev aluatethe
therapeut cpot
i entialofadr ugoracombi nati
on
ofdr ugsf ormanagi ngadi seasebasedonsucha
l
imit ed sampl esi ze.Bef orechoosi ng t hei deal
therapeut i
cagentf orthemanagement ofCOVI D-
19,r andomi zedcl inicalcont rolstudiesshoul dbe
perfor medwi thasuf fi
cientst udypopul ation.

Ant
ivi
ral
Drugs
Sev eralclasses ofr outinel
y used ant i
vir
al
drugs,l ikeoseltalnivi
r( neuraminidaseinhibi
tor)
,
acyclovir,ganciclovir
,andr ibavi
ri
n,donothav e
any ef fecton COVI D-19 and,hence,ar e not
recommended ( l b7) . Osel tami
v i
r, a
neuraininidase inhibi
tor,has been expl ored in
Chinesehospi t
alsf ortreatingsuspect edCOVI D-
19cases,al t
houghpr ovenef fi
cacyagainstSARS-
CoV-2issti
l
llacki
ng forthisdrug (
7).The iH
vi
tr
oant
ivi
ral
potent
ial
ofFAD-
appr
oveddr v
ugs,i
z.,
tIs<s› ’
ti
ltt
heocct ii
’
i’
<ri
ceoIi’
<>J i
iai
‹›
i‘
anet
car diovascul aradv er
se ef f
”ects.Hence,as a
caut ionar yappr oach,i tisbet t
ert or ecommend
the use of NSAl Ds as t he fir
st-l
ine opt i
on for
managi ngCOVI D-19sy mptoms( 302).Theuseof
cor ti
cost eroidsinCOVID-19patientsi ssti
l
lamat t
er
ofcont roversyandr equir
esf unhersy stematic
clinicalstudies.Theguideli
nesthatwer eputf
orward
tomanagecr i
ticall
yilladult
ssuggestt heuseof
sy stemi c cor ti
costeroi
ds i n mechani cal
ly
vent il
ated adul ts wi th ARDS ( 303) . The
gener alized use of cor ti
costeroi ds i s not
i
ndi cated i n COVI D-19,si nce ther e are some
concer ns associ at ed wi th t he use of
conicost eroidsi nvi ralpneumoni a.
St em cel lt
her apy
usingmesenchy malst ewcel ls(MSCs)i sanot her
hopef ulstrategy t hat canbeusedi nclinicalcasesof
COVI D-19 owi ng to i
ts pot ential
i
mmunomodul at Ory capaCi t
y.I t way hav e a
benef i
cialroleinattenuat i
ng t hecytoki nestormt hat
i
s obser ved i n sev ere cases of SARS- CoV-
2infection,t hereby r educing mor tality
.Among
thedi ff“
er entt ypesofMSCs,expandedumbi l
i
cal
cord MSCs can be consi der
ed a pot ential
therapeut icagentt hatr equir
esf urtherv alidation
formanagi ngcr i
ticallyill
COVI D-19pat ients(304) .
Rcpur
posedbr
oad-
spect
rumant
ivi
ral
drugs
Insuchc as eswher ethepat ient sprogr es st owar d
respi rator yfailureandbecomer efract or ytoox ygen
ther apy ,mec hani calv entilationi snecess itated.Th
e COVl D-19-
i
nducedsept icshock canbemanagedby
prov idingadequat ehemody nami csuppor t(
299) .
Sev er alclas ses ofdr ugs ar ec urrent l
y bei ng
eval uat edf ortheirpot ent ialther apeut icact ion
agai nst SARS- CoV- 2.Ther apeut i
cagent st hathave
anti-SARS- CoV- 2ac ti
v i
tyc anbebr oadl yclass ifi
ed
i
nt ot hreecat egor ies: drugst hat bloc k virusent ry
i
ntot hehos tcell,
dr ugst hat block v iralr epl i
cation
as wel l
asi tssur vivalwi thint hehost cel l
,and dr ugs
that attenuat etheex agger atedhost immuner es po
nse
(300) .Ani nflammat or ycy tok i
nest onei scommonl
yseeni nc ri
ticall
y il
lCOVI D- 19pat i
ent s. Henc e,they
may benef itf rom t he use of t imel y ant i
-
i
nflammat i
on treat ment .Anti
-
i
nflammat oryther apy usi ngdr ugs
l
ikegl ucocor ticoids, cytok i
nei nhibi tor s,JAK
i
nhi bi tors,andchl or oqui ne/ hydr ox yc hlor oquine
shoul dbedoneonl yaf teranal yzingt her is k/benef i
t
ratioinCOVI D-19pat ient s(301) .Ther ehav enot
beenany studiesc oncer ningt heappl i
cat ionof
nonst
eroidalanti
-i
nfl
ammat ory
drugs(
NSAI D)t
o
COVID-19-i
nfectedpati
ents.
However,
reasonable
pi
ccesofevidenceareavai
l
ablet
hatl
inkNSAID
lfi
i
precauti
oii
i
ii
ii
icasiweso› v
ingtotheuni‹i
ioi
inatur
e
of t his nov el v irus ( 36, 189) . Presentl
y,
themaincourseoftreatii
i
entforseverel
yaff
ectedSA
RS-CoV-2pat i
entsadmi tt
edt ohospi t
alsincl
udes
mechani calventil
ation,intensiv
ccar euni t(I
CU)
admi t
tance, and sympt omati
c and
suppor t
ivether apies.Addi tionally,RNAsy nthesis
i
nhi bitors( lami v
udi ne and t enof ov irdi sopr oxil
fumar at
e) ,r emdesi vir
,neur ami nidase i nhibit
or s,
pept ide (EKl ),ant i-i
nflammat or y dr ugs,abi dol,
and Chi nese t
radi ti
onal medi cine
(Lianhuaqi ngwen and ShuFengJi eDu capsul es)
coul daidi nCOVI D- 19treatment .Howev er ,f
urther
cli
nical tr
ials are being
car r
iedout concer ningtheirsafet y
andef li
cacy (
7).It
mi ghtr equi remont hst oay ear(s)t odesi gnand
dev elop ef fecti
ve dr ugs, t her apeut ics, and
vacci nes agai nst COVl D- 19, wi th adequat e
ev al
uat onandappr
i ovalf rom r egul atorybodi es
and mov ing t ot he bul k pr oduct ion ofmany
mi ll
ionsofdosesatc ommer ciall ev elst omeet
thet i
mel ydemandofmasspopul ationsacr oss
the globe (9) . Cont i
nuous
effor t
sareal sowar rantedtoident i
fy andassess
viabledr ugsandi mmunot herapeut icr egimens
thatr eveal edpr ov enpot encyi ncombat ingot her
v
iralagent
ssimi
lart
oSARS-CoV-2.
COVID-
19pat
ient
sshowi
ngsev
eresi
gnsar
e
treatmentf orMERS-andSARS- CoV i nf ections,
and themai nfocusi ncli
ni calsct ti
ngsremai nson
l
esseni ngclinical signsandpr ov idingsuppor ti
vecar e
(183- 1S6).Eff ect ivedrugst omanageCOVI D-
19pat ientsi ncl uder eirdesiv i
r,lopi nav i
r/ritonav ir
alone or in a bl end wi th i nterferon bet a,
conv alescent pl asma, and monocl onal
ant i
bodi es( MAbs) ;
howev er,ef ficacyandsaf et y
i
ssuesoft hesedr ugsr equi readdi t
ionalcl i
nical
tri
als( 187,2S1) .A cont r
ol l
ed t rialofr i
tonav ir-
boost ed l opi nav ir and i nterfer on al pha 2b
treatmentwasper formedonCOVI D-19
hospi tali
zed pat i
ent s
(Chi CTR2000029308) (185) .I naddi ti
on,t heuse
ofhy drox ychl or oqui neandt ocili
z umabf ort hei r
pot ential r
ol e i
n modul ating
i
nf l
ammat ory responsesi n the
l
ungsandant iv i
ral effecthas bccnpr oposed
anddi scussedi nmany researchar ticles.Stil
lnof
, ool -
proofcl i
nical trialshav ebeenpubl ished( 194, 19t i
,
197, 261—272) . Recent ly, a cl ini
cal t rial
conduct ed on adul tpat i
ent s suf fering f rom
sev ereCOVI D- 19r eveal ednobenef i
tofl opi nav ir
-ri
tonav i
rtreat mentov erst andar dcar e( 273) .
Theef f
or tstocont r
olSARS- CoV- 2infection
uti
li
ze defi
ned st
rat
egies as fol
lowed agai
nst
MERS
andSARS,al
ongwit
hadopti
ngandstr
engtheni
nga
st i
'ainofMy cobact e1‘ i
iii
rboi s.ñtp’csci i
t,
i1r'
cemen
clinicalt i
ialshav ebeenr egist eredt oev aluatet he
prot ectiver oleofBCGv acci nat i
on agai nstSARS-
CoV- 2(363) .Recent ly,acohor tstudy wasconduct ed
toev aluat ethei mpact ofchi ldhoodBCGv accination
i
n COVI D- 19 PCR posi tivityr ates. Howev er,
chi l
dhood BCGv acci nat i
on was f ound t o be
associ atedwi thar ateofCOVI D-19- positi
vet est
resul tssi mi lart ot hatoft henonv acci natedgr oup
(364) .Fur therst udi esar er equi red to anal y ze
whet herBCGv acci nat ioni nchi ldhoodcani nduce
pr otect i
veef fect sagai nstCOVI D-19i nadul thood.
Popul ation genet i
c st udies conduct ed on 103
genomes i dent i
fied t hatt he SARS- CoV- 2v inis
has ev olved i ntot wo maj ort y pes,L and S.
Amongt het wot y pes,Lt y pei sexpect edt obe
themostpr ev alent( -
70%) .f ollowedbyt heSt y pe
(-30%) ( 366) .Thi sf indi ng has a si gni fi
cant
i
mpactonourr acet odev elopani dealv acci ne,
since t he v acci ne candi datehastotar get
bot hstrainst obeconsi der ed effectiv e.
At present ,
thegenet icdi fferencesbet weent heLand
St y pes ar ever ysmal landmaynotaf f
ectt he
i
mmune r esponse.Howev er,we can ex pect
fur t
hergenet i
cv ariationsi nt hecoi ningday sthat
coul
dleadt
otheemer
genceof
newst
rai
ns(
367)
.
on i ts abi l
ityt o pr ov i
de pr ot ection notonl y
agai nst
present ver sionsof thev i
rusbut al sot heonest hatar e
l
ikely t o emer ge i n t he f ut ure. Thi s can
beachi ev ed by i dent if
y i
ng ant i
bodi es t hatcan
recogni zer elativelyconser v edepi t
opest hatar e
mai ntai nedassuchev enaf t ert heoccur renceof
consi der abl e v ariations ( 362) . Ev en t hough
sev eralv acci necl inicalt r
ial
sar ebei ngconduct ed
around the wor l
d,
pregnant womenhav ebeencompl etelyexcl uded
from t hesest udi es.Pr egnantwomenar ehi ghly
vulner abl et oemer gingdi seasessuchasCOVI D-
19duet oal terat i
onsi nt hei mmunesy stem and
otherphy siologi calsy stemst hatar eassoci ated
wi t
h pr egnancy . Ther efore,i n t he ev ent of
successf ul v acci ne dev el opment , pr egnant
womenwi l
lnotgetaccesst ot hev accines( 361) .
Hence,i ti srecommendedt hatpr egnant womenbe
i
ncl udedi nthe ongoi ng v acci ne t ri
als, si nce
successf ulvacci nat ioninpregnancy wi l
lprotectthem
other ,fetus, andnewbor n.
Thehet er ologousi mmuneef fectsi nducedby
Baci ll
usCal met teGuér in(BCG)v accinat i
oni sa
promi si ngst rategyf orcont rol li
ngt heCOVI D-19
pandemi
c and requi
res f
urtherinvesti
gat
ions.
BCG
i
sawidel
yusedv
acci
neagai
nstt
ubercul
osisi
nhi
gh-
underpi‘
ecl i
ii
ie.i
11i‘
ii
ts(2'?
7).Sii
ii
ikir
l.
theWINO, oni ts
offi
cial
websi te,
hasment ionedadet ail
edl
ist of
COVI D-19 v aCcine agent s t hat ar e under
consider ati
on.Di fferent phases of t ri
al s ar e
ongoingf orli
veattenuat edvirusvaccines,
f or
mal deh
ydealum i nact i
vatedv accine,adenov i
rust ype5
vectorv accine,LNP- encapsul atedmRNAv accine,
DNApl asmi dv accine, andSpr otein,S-
trimer ,and
Ii
-Key pept i
de as a subuni t protei
nv accine,
among ot hers( 295) .The pr ocess ofv accine
development usual lyt akes appr oximat elyt en
years,int hecaseofi nacti
vatedorl i
veat t
enuat ed
vaccines,si ncei tinvolvest hegener ati
onofl ong-
term effi
cacy data.
Howev er ,t
hiswasbr ought downt o 5 y earsdur i
ng
theEbolaemer gencyf orviralvectorv acci
nes.I n
the urgencyassociatedwiththeCOVI D-19
outbreaks,
weexpectavaccineby t
heendof thi
syear (
343).Thedev elopmentofanef f
ectivev accine
againstCOVI D-19withhighspeedandpr ecision
i
st he combi ned result of adv ancement si n
comput ati
onalbi ol
ogy,gene sy nthesis,prot ei
n
engineeri
ng, and t
he
i
nv enti
onofadvancedmanuf acturi
ngplatforms( 342)
.
 Therecurr
ingnatureof
thecoronavi
rus
outbreakscal l
sf orthedevelopmentofapan-
coronavir
us vacci
nethatcanpr
oducecr
oss-
react
iveanti
bodies.
detect ablescr umSARS- CoV- ncut r al
izingant i
bodi cs
(170).Ant igeni cdeter minant sit espr esentover Sand
N st ruct uralpr oteins ofSARS- CoV- 2 can be
explored assui table v acci necandi dates ( 294).
I he As
nt ian popul at i
on,S,E,M, andN pr ot eins
ofSARS-CoV- 2ar ebei ngt ar get edf ordev elopi ng
subuni tvacci nesagai nstCOVI D- 19( 295) .
Thei dent if
icationoftheimmunodomi nantregi
on
amongt hesubuni tsanddomai nsofSpr otei nis
cri
ti
calf ordev elopinganef f ect i
v ev accineagai nst
thecor onav irus.TheC- ter mi naldomai noft he
S1subuni ti
sconsi der edtheimi niinodomi nant r
egi on
oft hepor cinedel tacor onav ir
usSpr otein( 171) .
Similar l
y ,f urtheri nvestigat ions ar e needed t o
determi ne t he i mmunodomi nant r egi ons of
SARS-CoV- 2f orf acili
tati
ngvacci nedevel opment .
However ,
our previousat tempt stodevel opa
univer salv acci net hati sef f ect ivef orbot hSARS
-CoV andMERS- CoV basedonT- cellepi tope
similar i
typoi ntedoutt hepossi bi
lityofcr oss-
reactiv i
ty amongcor onav i
r uses( 172) .
That canbe
madepossi bleby select edpot ent ialvacci netarget s
thatar ecommont obot hv ir
uses.SARS- CoV- 2
hasbeenr epor tedt obecl osel yr elatedt oSARS-
CoV( 173, 174) .
Hence, knowl edgeandunder standingof
imi nunot hcr apeut ics,and ant i
viraldr ugs,hav e
been ex ploited agai nst t he pr ev i
ous CoV
out breaks( SARS- CoVandMERS-
CoV) (S,104, 164—167) .
These v aluabl e opt ions hav e al ready been
eval uatedf ort heirpot ency ,efficacy,andsaf ety,
alongwi t
hsev eralot hert ypesofcur rentr esearch
thatwi llf uel oursear ch f ori dealt her apeuti
c
agent sagai nst COVI D- 19( 7,9,19,21,36) .The
primar ycauseoft heunav ail
abilit
yofappr oved
and commer cial
vacci nes, drugs, andthei '
apeut i
cstocount er the
ear l
ierSARS- CoVandMERS- CoVseemst oowet o
the l esser at tention of t he bi omedi cine and
phar maceut icalcompani es,ast heset woCoVs
didnotcause much hav oc,gl obalt hr eat,and
pani cl ike t hose posed by t he SARS- CoV-2
pandemi c( 19) .Mor eov er,f orsuch out break
situations, the
requi r
ement forv accinesandt herapeut i
cs/ dr ti
gsexi
stsonl yf oral imi t
edper i
od,unt iltheout breakis
cont rolled. The pr opor ti
on of t he human
popul at i
on i nf ected wi th SARS- CoV and MERS-
CoVwasal somuchl oweracr osst hegl obe, fai
li
ng
to at tractdr ugand v acci ne manuf act ur ers and
producers.Therefore,byt he ti
me an ef f
ecti
ve
drugorv accineisdesignedagainstsuchdisease
outbreaks, t
he vi
rus would have
beenconuolledbyadopti
ngappropri
ateandst
ri
ct
madet odesi gnanddev elopv acci nesf orCoV
i
nf ection, most ly by t arget i
ng t he spi ke
glycopr otein.
Nev enhel ess,owi ngt oextensiv ediversity i
n
antigenicv ariants,cr oss-protectionr ender edby
thev accinesi ssi gnificantlyl i
mi t
ed,ev enwi thin
thest r
ainsofaphy logenet icsubcl ust er( 104).
Duet ot hel ackofef fecti
v eant iviralt herapyand
vacci nes i nt he pr esentscenar io,we need t o
dependsol clyoni mpl ement ingef fect i
v ei nfect i
on
controlmeasur est ol essent her iskofpossi ble
nosoconi ialt ransmi ssion ( 6S).Recent ly,t he
recept orf orSARS- CoV- 2wasest abl ishedast he
human angi otensi n-conv erti
ng enzy me 2
(hACE2) ,andt hev ir
uswasf oundt oent ert he
hostcel lmai nlyt hroughendocy t
osi s.I twasal so
foundt hatt hemaj orcomponent st hathav ea
cri
t i
calr olei nv iralent r
yi ncludePI Kf y ve,TPC2,
andcat hcpsi nL.Thesef i
ndingsar eci 'iti
cal , si
nce
thecomponent sdescr i
bedabov emi ghtactas
candi dates f orv acci nes ort her apeut ic dr ugs
againstSARS-CoV- 2( 293).
Themaj orityoft het reat mentopt i
onsand
strategiest hatar ebei ngev aluatedf orSARS- CoV-
2( COVI D- 19)hav ebeent akenf rom ourpr ev i
ous
exper
iences int r
eatingSARS-
CoV,MERS- CoV,
and
other
emer gi
ngv
iral
diseases.
Sever
alt
her
apeuti
c
super spr eaderpot ent i
alofSARS- CoV- 2/ COVI D
war rantf ullex pl
oi t
at i
on ofr eal -
time di sease
mappi ngbyempl oy i
nggeogr aphi calinformat i
on
sy st
ems( GIS),such ast heGISsof twar e Kosmo
3.1, web- basedr eal-ti
me tools and
dashboai •ds,apps,andadv ancesi ni nf
or mat ion
technol ogy( 356-359) .Resear cher shav eal so
dev elopedaf ewpr edict i
ont ool s/model s,such
ast hepr edictionmodelr i
skofbi asassessment
tool ( PROBAST) and cr i
t cal appr
i ai sal
anddat aex t
ractionf orsyst emat icreviews of
predi ctionmodel ingst udies( CHARMS) ,whi ch
coul d ai di n assessi ng t he possi bilit
y of
get t
ingi nfectionandest i
mat i
ngt hepr ognosi s
i
npat ient s;however ,suchmodel smaysuf fer
from bi as i ssues and, hence, cannot be
consi der ed compl etely
mi stwor thy,whi chnecessi t
atest hedev elopme
ntofnewandr eliablepr edictors(360) .

VACCI
NES,
THERAPEUTI
CS,
AND
DRUGS
Recentl
yemer ged vi
ruses,such asZi ka,
Ebol
a,andNipahvi
ruses,
andt hei
rgr
avethrcats
tohumanshav ebegunar acei nex
plor
ingt he
desi
gning and
developi
ngof
advancedvacci
nes,
prophyl
act
ics,
ther
apeuti
cs,
anddr
ugregi
menstocounter
emergi
ng
i
i
ihi
s(34)
.I
T-LASTI
*sci
xcs as a st
nip1c,i
api
d,and
sensi t
ive diagnost i
c met hod t hat docs not
require sophi sticat ed equi pment or ski l
led
personnel ( 349). An i nter acti
v e web- based
dashboar df ort racki ng SARS- CoV- 2i n ar eal
-
ti
me mode has been desi gned ( 238) .A
smar t
phone-integrat ed home- based poi nt-of -
caret esting( POCT)t ool,apaper -
basedPOCT
combi nedwi thLAMP,i sausef ulpoi nt-
of -care
diagnost i
c( 353).AnAbbot tI D Now COVI D- 19
mol ecular POCT- based t est,
usi ngisot her mal
nucleicaci dampl i
f i
cat i
ont echnol ogy ,hasbeen
designedasapoi nt-of -
caret estf orv eryr apid
detect i
onof SARS- CoV- 2i nj ust5mi n( 344) .A
CRISPR- based SHERLOCK ( speci fi
c hi gh-
sensi t
ivi
ty enz ymat ic r epor t
er unl ocki ng)
diagnost i
cf orr api d det ection of SARS- CoV- 2
without t he r equi r
ement of speci alized
i
nst rument ati
onhasbeenr epor t
edt obev ery
usefulinthecl i
nical diagnosi sofCOVI D-19( 360) .
A CRI SPR- CasI2-basedl at eralf l
ow assayal so
hasbeendev elopedf orrapi ddet ect i
onofSARS-
CoV- 2( 346).Ar t
ificialintelli
gence,bymeansof
at hree-di mensi onaldeep- l
ear ningmodel ,has
been dev el
oped f or sensi ti
ve and speci fi
c
diagnosisofCOVI D-
19v i
aCTimages(332).
Trackingandmappingoft
her
isi
ngi
nci
dence
rates,di sease out
breaks,communit
y
infect ion,l imi t
ingi tsuset ot heear lierst agesof
i
nf ect ion.Sev er allabor ator i
esar oundt hewor l
d
ar e cur rent ly dev elopi ng ant ibody -
based
diagnost ict est sagai nstSARS- CoV- 2(157) .
Chest CTi sani dealdiagnost ictool for i dent if
ying
viralpneumoni a.Thesensi tivityofchestCTi sfar
super i
ort ot hatofX- r
ayscr eeni ng.ThechestCT
findings associ atedwi th COVI D-19- i
nfected
pat i
ent si ncl udechar act eristicpat chyi nfil
tr
ation
thatl at erpr ogr essest o gr ound- glassopaci ti
es
(158) . Ear l
y mani fest ations of COVI D-19
pneumoni ami ghtnotbeev identi nX- raychest
radiogr aphy . I n such si tuations, a chest
CTex ami nat ion can be per f
or med, as i ti s
consi der ed hi ghly speci fic f or COVI D-19
pneumoni a( 118) .
Thosepat ientshav i
ngCOVI D-19
pneumoni awi llexhi bitt het ypicalgr ound- glass
opaci ty in thei r chest
CTi mages( 154) .Thepatient sinfect edwi th COVI D-
19hadel ev atedpl asmaangi otensi n2l ev s.The
el
l
ev elofangi otensi n2wasf oundt obel i
near l
y
associ at ed wi th v i
ral l oad and l ung i njury,
i
ndi cat ingi tspot enti
alas a
diagnost icbiomar ker(
121) .ThechestCT i magi ng
abnor mal it
ies associ ated wi th COVI D-19
pneumonia have also been observ
ed even
i
nasymptomati
cpat
ients.
Theseabnor
mal
it
ies
CoY- 2.butt hecui ‘i
’enti ‘
aieofspi ‘
eadl imi tsi ts
useduet ot hel ackofdi agnost icassayki ts.Thi s
wi l
l f urther result i
nt he ext ensi ve
transmi ssionof COVI D- 19,sinceonl yapor ti
onor
suspect ed casescan be di agnosed. I n such
situations,conv ent i
onalser ol ogi calassay s,l ike
enz yme- l
inkedi i
ninunosor bent assay ( ELI SA) ,
thatar e speci fict o COVI D- 19 l gM and l gG
ant i
bodi es can be used as a hi gh-
throughput alternat i
v e(149).At present ,t
her eis no
diagnost i
cki tav ailablef ordet ectingt heSARS-
CoV- 2 ant i
body ( l50) . The speci f
ic ant ibody
profilesofCOVI D-19pat i
ent swer eanal y x ed, and
i
twasf oundt hatt hel gM l ev ell astedmor et han
1mont h,i ndicatingapr olongedst ageofv irus
replicationi nSARS- CoV-2-inf ect edpat i
ent s.The
IgGl ev elswer ef oundt oincr easeonl yi nt hel ater
stagesoft hedi sease.Thesef i
ndi ngsi ndi cat et hat
thespeci ficant i
bodypr ofil
esofSARS- CoV- 2and
SARS- CoVwer esi mi lar(325) .Thesef indi ngscan
be ut il
ized f or t he dev elopment of speci fi
c
diagnost i
c tests agai nst COVI D-
19andcanbeusedf orrapidscr eeni ng.Ev en t hough
diagnost i
c t est ki t
s ar e al ready av ailable
thatcandet ectthegenet i
csequencesofSARS- CoV-
2( 95) ,t heirav ail
abi li
tyi s a concer n,as t he
numbei• of
COVID-
19casesisskyr
ocketi
ng(l
55,
157).
A
majorproblemassoci
atedwi
tht
hisdi
agnosti
cki
ti
s
 l
cthal
cli
ii
l
lcid CL cJdi
ll
lt
ibC›‹
ti
cs i
ii
i
iy pl.
iya
cruci
al r ole i n enhanci ng protect
ive
humoralresponsesagai nstt heemergingCoVs
byaimi ngappr opr
iateepi t
opesandf uncti
onsof
thc S protei
n. Thecross-
neut rali
zat i
onabili
tyofSARS- CoV RBD-speci fi
c
neut rali
zi ng MAbs consi derablyr eli
es on t he
resembl ance bet ween t hei
r RBDs; t heref ore,
SARS- CoVRBD- speci fi
cant i
bodi escoul dcr oss-
neut rali
zedSLCoVs, i
.e.,
bat -
SL- CoVst r
ainWI VI
(RBD wi th eightami no acid di fferences f ront
SARS-CoV)butnotbat -SL-CoVst r
ainSHC0l 4
(24ami noaci ddi f
ferences)( 200) .
Appr opr iat
eRBD- speci fi
cMAbscanbe
recogni zed bya r elati
ve anal ysis ofRBD of
SARS-CoV- 2tot hatofSARS- CoV,andcr oss-
neut rali
z ing SARS- CoV RBD- speci fi
c MAbs
coul d be expl ored
fortheiref fecti
venessagai nstCOVI D-19
andf urtherneedt obeassessedcl i
nical
ly .The
U.S. bi ot echnology company Regener on i s
attempt ing t or ecogni ze pot entand speci fi
c
MAbs t o combat COVI D-19. An i deal
therapeut icopt i
onsuggest edf orSARS- CoV- 2
(COVI D-19) i s t he combi nation t her apy
compr ised of MAbsand t hedr ugremdesi vir
(COVID-
19)
(20l).
TheSARS- CoV-speci
fi
c human
MAbCR3022i sf oundt obindwithSARS- CoV-
2
RBD,i
ndi
cat
ingi
tspotent
ial
asather
apeuti
cagent
thisisbot hchal lengi ngas wel l
as t ime- consumi ng
duet ot hepr esentext entofi nfection( 226) .The
cur r
ent scenar io demands effective
i
mpl ement at i
on of v i
gor ous pr ev ent ion and
cont rolst rategi es owi ng t ot he pr ospectof
COVI D-19f ornosocoi ni
al infections( 6S) .Fol l
ow
-upsofi nfect edpat i
ent sbyt elephoneonday7
and day14ar eadv ised t o av oid anyf urther
unint entional spr ead or nosocomi al
transmi ssion ( 312) .The av ail
abilityofpubl i
c
dat a set s pr ov i
ded byi ndependentanal yti
cal
teamswi llactas r obustev i
dence t hatwoul d
guideusi ndes i
gni ngi nter v
ent i
onsagai nstt he
COVI D-19 out break. Newspaper
repor tsandsoci almedi acanbe used t oanal yze
andr econst ructt hepr ogressi on of an out br eak.
They canhel pust oobt ai
ndet ai
ledpat ient-l ev el
dat ai nt heear lyst agesofanout br eak( 227) .
Immedi ate t rav el r estricti
ons i mposed by
sev eral count ries mi ght hav e cont r
ibut ed
significantlyt opr event i
ngt hespr eadofSARS-
CoV- 2gl obal ly( 89, 225) .Fol l
owi ngt heout br eak,
at empor arybanwasi mposedont hewi ldli
fe
trade,keepi ngi nmi ndt hepossi bler olepl ay ed
bywi l
dani malspeci esi nt heor iginofSARS-
CoV-2/COVI
D-19 (147).Maki ng a per manent
and bold decisi
on on t he t r
ade of wi ld
ani
malspeci
esi
snecessar
ytoprevent
thepossi
bil
i
ty
ii
npoitance.becausethe sti
'ai
nontl
ici
imental
»ell
-
beingwi llaiTecttheiratt
enti
on,concentrat
ion,
and deci si
on-making capaci t
y. Hence, f or
control of t he COVI D-19 out break,
rapidstepsshouldbet akentoprotectthemental
heal
thofmedi
cal
wor
ker
s(229)
.
Sincet heli
v i
ngirair
rnal
ssoldi
nthewet mar ket
are suspect ed t o be the i
ntermediate host
ofSARS-CoV- 2,thereisaneedforstrengthening
the regul atory mechani sm forwi ld ani mal
trade ( I3).The t otalnumberofCOVI D-19
conf i
rmedcasesi sonacont inuousr i
seand
thecur er at
ei sr elat
iv yl
el ow,maki ngdi sease
controlvery di f
fi
cultto achi
eve. The Chi nese
gov ernmenti smaki ng conti
nuous ef f
or t
st o
contain the di sease by t aki
ng emer gency
controlandpreventi
onmeasur es.
They havealr
ea
dy
buil
tahospitalf
orpatientsaff
ectedbythisv
irusan
d ar e currently building several wor ef or
accommodat i
ngt
heconti
nuouslyincreasi
ngi
nfec
ted popul
ati
on(230).Theef fecti
v econtr
olof
SARS- CoV-
2/COVID-19requires high-
l
ev el
int
erv
entons l
i i
ke i ntensiv e cont act
traci
ng,aswel last he quarantineofpeopl e
wit
h suspectedinfection and the isol
ati
on of
i
nfected i ndi
v i
duals. The i mplementati
on
ofr
igorous contr
ol and pr
eventi
ve
measur est
ogether
mightcontr
olt
heR0number andreducethe
tr
ansmi ssi
onri
sk225. Consi t
hezoonoti
c
to ev aluate t he risk of f utur
e epidei v›ics.
Presently,licensed ant ivi
raldr ugsorv acci nes
againstSARS-CoV,MERS- CoV,andSARS- CoV- 2
arel acking.Howev er,adv ances in desi gning
anti
viraldr ugs and v accines againstsever al
other emer ging di seases wi l
l help dev elop
suit
abl ether apeuticagent sagai nstCOVI D-19i n
ashor tt i
me.Unt i
lthen,wemustr elyexclusiv ely
on vari
ous cont rol and prev ention
measur estopr eventthi
snewdi seasefr
ombecom
i
ngapandemi
c.
4VI
ROLOGY
Coronav iruses,af ami l
y ofvir
useswi t hint he
nidovir
usessuper fami ly,arefur thercl assifi
ed
accordingt othei rgener a,alpha-,bet a-,gamma-
anddeltacor onavi ruses( a-,
§-,
y-and6- ).
Amongt hose,alphaandbet aspeci esar ecapabl e
ofcont ami nati
ngonl ymammal s, wher eas
theothertwogener acani nfectbirds
1 1
andcoul dalsoinf ectmammaI s, *^ Twoof
thesegener abel ongt ohumancor onavi ruses
(HCoVs) :a-coronav i
ruses, whichcompr ise
humancor onavi rus229E( hcov229E) and
humancor onavi rusNL63( hcovNL63) ,and§-
coronaviruses,whi char ehumancor onavi rus
HKU1,humancor onavir
usOC43,MERS- COV
(knownasMi ddl eEast respi r
ator ysy ndr ome
coronavirus)andSARS- CoV( referredt oas
severeacut erespi ratorysy ndrome
1
coronav irus), ’

Thesev ereacut er espirat

orysyndromeCoV
-2(SARS- CoV- 2)
isnownamednov el COVID-
1
19( coronav i
rusdisease2019) .*Genome
sequenci ngandphy logeneti
cresearch
revealedt hattheCOVI D-19-
causingcor onavirusisabet a-
coronav i
rus
thatbelongst othesamesubt ypesas
SARSv i
rus,butst
ill
existsina
var
iant
group.
Ther
ecept
or-
bindi
ngsgener
egi
on
primaryant i
-geni
cepi t
opesmai nlythose
recognisedbyneutrali
singanti
bodies.ThespikeS-
protei
nbei nginaspikef
or missubjectedtoa
struct
uralr
ear r
angement pr
ocesssot hatfusing
theoutermembr aneoft hevi
ruswi t
hthehost-
cel
l
membr
anebecomeseasi
er1 20R
. ecent
SARS-CoVworkhasalsoshownthatt
he
membr aneexopepti
daseACEenzyme
(angi
otensi
n-conver
ti
ngenzyme)funct
ionsasa
COVID-19receptort
oenter
thehumancell1
.
‘

” HE

FI
GURE1
obser vedt hroughbot hinvi voandi nvit
ro
ex per iment s.Ther eisanenhancednasal
secr et i
onobser vedal ongwi thl ocaloedema
becauseoft hedamageoft hehostcel l,
whi chf ur t
her stimul atest hesy nthesisof
inflammat orymedi ator s.I naddi tion,these
react ionscani nducesneezi ng, diffi
culty
breat hi ngbycausi ngai rwayi nhi bit
ionand
elevat emucosalt emper at ure.Thesevi ruses,
whenr el eased, chieflyaf fectt helower
respi rat orytract,wi tht hesi gnsand
sympt omsexi stingcl ini cal l
y.Al so, t
he
virusf ur theraffectst hei nt est inal
lymphocy tes,renalcel ls, l
iver cellsandT-
lymphocy tes.Fur t
her mor e,t
hevi rusinduces
T-cel lapopt osis,causi ngt her eact i
onoft heT
-celltobeer r
atic,resul tingi nt hei mmune
syst em‘ scompl etecol apse24d25
l

5.
1Modeof
transmi
ssi
on
Infacti twasaccept edt hattheorigi
nal
transmi ssionoriginatedf rom aseafood
mar ket,whi chhadat raditionofsell
inglive
animal s,wher ethemaj or i
tyofthepat i
ents
hadei ther
wor kedor visi
ted,alt
houghupt onowt he
under standingoft heCOVI D-19tr
ansmi ssion
16
ri
skr emai nsincompl ete.I nadditi
on, while
thenewerpat ientshadnoexposur et othe
market
andsti
l
lgott
hevi
rusfr
omthehumanspr esent
ther
e,t
herei
sani
ncreasei
ntheout
breakof
ther e,thereisanincr easeintheoutbreakof
thisvi rust hroughhuman- to-
human
transmi ssi
on, witht hefactthatit
hasbecome
wi despr eadar oundt heglobe.Thisconfi
rms
thef actsi milartot he
previ ousepi demi cs,includingSARSand
MERS, thatt hiscor onavirusexhibited
pot ent ialhuman- to-humant ransmi ssi
on,
as
i
twasr ecent lydecl aredapandemi c
2
by WHO. ^

Respi ratorydr opletsarethemaj orcar r

ierfor
cor onavirust ransmi ssion.Suchdr opl ets
canei therst ay i
nthenoseor mout hor ent er
thel ungsvi at heinhaledai r
.Cur r
ent ly
, it
is
knownt hatCOVI D-19‘s
transmi ssionf romoneper son
toanot heralsooccur sthroughtouchi ngei the
rani nfectedsur faceor evenanobj ect.Wi th
thecur rentscant awar eness
ofthetransmi ssionsy stemshowever ,
airbornesaf et ymeasur eswithahigh-
ri
skpr ocedur ehavebeenpr oposed
i
nmany count ri
es.Tr ansmi ssi
onl ev el
s,
orthe
ratesfromoneper sont oanother ,
repor ted
differbybot hl ocationandi nteractionwi th
i
nvol vement ininfectioncontrol
.Iti
sst ated
thatev enasy mpt omat ici
ndividualsor those
i
ndivi
dualsi
ntheiri
ncubat i
onperiodcanacta
272
scarr
ierofSARS- CoV2. *Wit
ht he
dat
aandev idencepr ovided
byt
heCDC, t
heusual
i
ncubationperi
odi sprobabl y3t
o7day s,
sometimesbeingpr ol
ongedupt oeven2
weeks,andthetypicalsympt om occurrence
6.1Laborator
y t
esti
ngf
or
coronavir
usdisease
2019(COVI D-
19)insuspectedhumancases
Theassessmentof thepat i
ent swi
thCOVI D-
19shoul dbebasedont hecli
nicalfeat ur
es
and
alsoepidemi ol
ogicalfactors.Thescreening
protocolsmustbepr eparedandf ol
lowed
per
31
thenati
v econtext. Col l
ectingandtest i
ngof
specimensampl esf r
om t hesuspect ed
i
ndividual i
sconsideredtobeoneof themai n
pr
inci
plesf
orcont
rol
l
ingandmanagi
ngt
he
outbreakof thediseasei nacount r
y .The
suspect edcasesmust bescreenedt horough
yi
l nor dert odetectthevir
uswi t
hthehel pof
nucleicaci dampl i
ficati
ontestssuchasr ev er
setranscr iptionpol y
mer asechai nr eaction
(RT-PCR) .Ifacount r
yorapar t
icul
arr egi
on
doesnot
havethef aci l
it
ytotestt
hespeci mens, the
specimensof thesuspect edindividual
shouldbesent t
othenearest r
eference
32
l
abor atoriespert hel i
stpr ovi
dedbywuO,

It
isal
sorecommendedthat
thesuspect
ed
pati
entsbetest
edf
ortheot
herrespi
rat
ory
pathogensbyper formingther outi
ne
l
abor at
ory
i
nvest i
gationperthel
ocalguideli
nes,mai
nly
t
odi f
ferenti
atefr
omot hervi
rusesthati
ncl
ude
i
nfluenzavirus,parai
nfl
uenzavirus,
adenovirus,
weeks,
andthet
ypical
symptomoccurrence
f
romincubati
onperi
odtoi
nfect
iont
akesan
aver
ageof
12.
Sdays.
"

I
CALDI
AG OSI
Thesy mpt omsof COVI D- 19r emainver y
simi lar
tothoseof theot her respirat oryepidemi csin
thepast ,whichi ncludeSARSandMERS,
but
her ether angeof sympt omsi ncludesmi ld
rhinitist osept icshock.Somei ntestinal
distur banceswer er epor tedwi t
ht heot her
epidemi cs,but COVI D-19wasdev oidof such
sympt oms.Whenex ami ned, unilateral or
bil
at er alinvolvementcompat i
blewi thviral
pneumoni ai sobser vedint hepat i
ent s,and
bil
at er al mul t
iplel obul arandsub-
segment alconsol idati
onar easwer e
obser vedi npat ientshospi tali
sedi nt he
i
nt ensi v ecar euni t
.
Comor bidpat ient sshowedamor esev ere
cli
ni cal cour sethanpr edict edfrompr ev i
ous
epidemi cs.Di agnosi sofCOVI D-19i ncl udes
thecompl etehi stor yof t
ravelandt ouch,
withl abor atoryt est i
ng.I tismor epr ef erable
tochooseser ol ogical screeni ng,
whichcanhel
ptoanal
yseeventhe
asymptomatici
nfect
ions;
several
ser
ologicalt
est
sareinprogr
essf orSARS-
CoV-2.
°'
4.
2Vi
ral
repl
i
cat
ion
Usual lyr eplicat i
onofcor onavi rusoccur s
wi t
hint hecy topl asmandi sclosel y
associ atedwi thendopl asmi cr eticulum
andot her cellularmembr aneor ganel les.
Humancor onavi rusesar ethought toinvade
cells,pr i
mar il
yt hroughdi fferent r
ecept ors.
For 229EandOC43, ami nopept idase- N(AP
-N)andasi ali
caci dcont ainingr ecept or,
respect i
vel y
, wer eknownt of unctioni nthis
role.Af t
ert hevi r
usent erst hehostcel land
uncoat ingpr ocessoccur s,thegenomei s
transcr ibed, andt hen, transl ated.A
char act eristicfeat ureof r
epl i
cat i
oni sthat all
mRNAsf or manencl osedgr oupof typical3’
ends; onl y t
hespeci al por t
ionsof the5’ ends
aret ransl ated. Intotal,about7mRNAsar e
produced.Theshor test mRNAcodesandt he
other scanexpr esst hesy nthesi sof
anot hergenomesegment fornucl eopr otein.
At t
hecel lmembr ane, thesepr oteinsar e
collect edandgenomi cRNAi si nitiatedas
amat ur epar ticlety peby burgeoni ng
fromi nt ernalcel l
membr anes. * 2y23

5PATHOGENESI
S
Coronavirusesaretr
emendously
preci
seandmat urei
nmostoftheai
rway
epit
hel
ialcell
sas
observedthroughbothi
nvi
voandinv
itr
o