Lost Cause Antivirals Etc of Topical Interest

D Grant PHD in Chemistry, Turriff, UK

THIS IS NOT MEDICAL ADVICE
I

Key ref. ”Polyanions – a lost cause in the fight against

HIV and other virus diseases”, Lüscher-Mattli M et al.
Antivir. Chem Chemother 2006 Jul 11 (4) 249-59
Heparan sulphate viral entry blocking.
Needs improved method (e.g. by using nanoparticle delivery) of getting same in vivo activity
as that achieved in vitro.
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Milk -derived proteins lactoferrin etc.

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Some of these ideas may benefit current and future
pandemic threats using the broad spectrum antivirals
which act faster than acquired immunity.

[During the AIDS crisis sulphated polysaccharides were

found to offer broad spectrum antiviral effects against
HIV-1 and II and Likely also effective against respiratory
syncytial virus, a major cause of childhood lung
congestion/damage.
also showed anti syncytium effects (which could seriously impair
conventional B and T cell related immunization) .
It seems likely that the anti-HIV polysaccharides also inhibited a range of other viruses which
like HIV-1 use complex cytokine/chemokine evasion techniques (cf. PMID 26177523)

Long list of possible uses against other coated viruses which gain entry via host
heparan sulphate.

Those (heparin-like) substances with anti-HIV activities

may also be effective against heparan sulphate
affforded COVID19 entry to host (cf. C Mycroft-West et
al 2020 “The 2019 coronavirus surface protein Spike S1
receptor binding {domain undergoes conformational
change upon heparin binding a possible anti SARS-CoV-
2 potential because of their mode of entry to the host
is via cell surface heparan sulphate}.
A perceived problem with potential use conventional
heparin as a broad spectrum antiviral is that UFH is also
a blood anticoagulant. But there are available non-
anticoagulant heparin including low molecular weight
varieties.
Also used for many years heparinoids such as pentosan
poly-sulphate SP54 (Elmiron US FDA approved for
interstitial cystitis). This is obtained from birch wood
shavings from which the xylans are extracted using
conventional techniques and then sulphated using
pyridine containing medium.
A similar technique was applied to marine algal (e.g.
Palmaria)polysaccharides studied at Aberdeen
University at around 1990; a highly active anti-HIV
agent was obtained. Sufficient quantities and funding
for a clinical trial were however not obtained. A proof
of concept was however established.
Such an academic study looking at anti-HIV activities
of a range of sulphated molecules posted online in
2010
Is available at
35999390/

This lists a
“Old Anti-HIV Study Refs Antiviral Drug Hiv/Aids-scribd”
range of starting natural polysaccharides which on
sulphation and fractionation might provide the wanted
types of antivirals.

A related project was oilfield anti-scale polysaccharides

which strangely were apparently also antiviral.
A number of other sulphated organic molecules were
tested for anti-HIV activity at the same time.
The sulphated polysaccharide broad spectrum antiviral
avenue was researched by a number of groups
internationally (cf e.g. De Clercq 1990 TIPS 11 198);
Clinical trial of low molecular weight heparin in
advanced AIODS (1996) showed CD4 stabilized; self
administration was possible to treat AIDS patients on a
long term basis at low cost Chem Abs 125 316373) but
eventually was however not pursued twenty five years
ago as alternative highly effective drugs specific for the
target virus had been discovered (e.g. AZT Ziduvudin)
and were successful when used in a cocktail..

The Linus Pauling anti-common cold high ascorbate

hypothesis.
A possible explanation for the putative broad spectrum
anti-viral effect of high dose ascorbate is the
upregulation of heparan sulphate biosynthesis with
increased sulphation, i.e. a possible creation of
‘endogenous circulating heparin’ with anti-viral
properties
[This phenomenon had been studied by H Engleberg
from the 1960s and suggested to offer therapeutic
potential for a range of diseases].

Why do agents which may have beneficial effect in

Alzheimer’s disease also possibly inhibit coronavirus
infections?
Cf. Chloroquine is reported to inhibit amyloid tau
plaque and fibril formation and also to be a candidate
anti-COV-19 agent.
Cf. PMID3 2147496; 32171740
Hydroxychloroquine is less toxic but of apparent similar
efficiacy.
Could this be because amyloid fibrils can aid viral entry
to the host? This has been reported for HIV infection.
Cf. PMID 24832047.
Cf. “The surprising role of Amyloid Fibrils in HIV
Infection PMID 24832047

Further COVID-19 notes 27/3/20

The innate immune response to severe acute
respiratory syndrome (SARS) coronavirus (CoV)
infection putatively critically involves the viral
glycoprotein interaction with Mannose Binding Lectin
(MBL) [a pattern recognition molecule (capable of
genetic polymorphism which might predict those at
greatest risk); MBL is an acute antibody factor before
the specific antibody response. A study of n=561 SARS
vs 1188 controls indicated (PMID 15838797) that MBL
deficiency is a possible susceptibility factor in the
acquisition of SARS viral infection.
Does this also apply to COVID-19?
A study of MBL in HIV-1 with genotype analysis
suggests polymorphism could predict susceptibility to
HIV-1 infection (PMID 19796822).
A study in mice with Ebola virus infection showed that
therapeutic recombinant MBL countered this infection
PMID 21288816) thus suggesting how a broad
spectrum antiviral therapy might be facilitated.

Corpus ID 46424068 In vitro evaluation of the

synergistic antiviral effect of ACE-M {acemannan (a
long-chain poly-dispersed beta(1,4) acetylated
mannan) with anti-HIV AZT (azidothymidine) and
acyclovir (ACY).

The use of mannan adjuvant (100/1 inactivated virus)

apparently might (PMID25887952) allow pandemics
arising from mutation of e.g. H1N1 to be averted by
avoiding the otherwise too-slow development of a new
specific vaccine.

Phosphonates
Phosphonated proteins bind better to aluminium
hydroxide adjuvant to increases vaccine potencies (F
Lu et al Vaccine 2013 31 4362.

Phosphorous acid may do likewise.

Phosphorous forms insoluble aluminium carbonate
double salts of possible use in vaccines.

Nucleoside Analog Anti-Virals

Acyclic nucleoside phosphonates are well known as a
key class of antiviral drug (via inhibition of nucleic acid
synthesis)
(cf. PMID 16264436).(Cf. tenofovir for the prevention
of AIDS). The non-mammalian phosphonate with P-C
replaces the P-O-C groups needed to allow nucleic acid
polymerases to function
It was reported in 2018 (Gaiuai et al.) that the viral
polymerases in SARs-COV RdR8 are inhibited by a
modified nucleoside phosphonate approach.

Bisphosphonate use as adjuvant like molecule(?)

“Phospho-antigens”.
Zoledronic acid plus IL-2 improved the
immunocompetence of HIV-1infected persons (AIDS 23
555) via Vγ9Vδ2 T cells.
CORONAVIRUS SPECIFIC TREATMENTS
doi/10.1002/jmn.25707
Coronavirus protease inhibitors
Chymotrypsin and Papain are encoded by coronavirus
Cinaserin Flavenoids Diarylheptanoids Spike (S)
protein, angiotensin converting
enzyme 2 (ACE2) blocker
Chloroquine Promazine Nicotinamide Emoden
Cinancerin (serotonin reuptake inhibitor)
Antivirals (anti-HIV) Lopinavin and Remesivir;
Nelfisavir Arbidol
NITRIC OXIDE (NO) (Cf. NO donor S-nitroso-NAc
penicillamine inhibits SARS-COV V concentration
dependently (Akerström et al.)
NO works under hydrogen sulphide (H2S) control
(Insert H2S per se is also a likely potent antiviral
Cf. H2S ex GYY4137 combats respiratory syncytial virus
airway infection PMID 2731446; 32107411; cf. also
Bazhanov N et al. SciRep 7 Art No. 41029(2017);
active against H1N1).
Alpha lipoic acid (is a naturally occurring disulphide
which enhances glutathione)
Estradiol or phytoestrogen
Cf. more male fatalities in SARS-CoD infection
Mucroporin-M1 (scorpion)
Resveratrol (red wine)
Ozone therapy H Robins web
Shilajit
J Med Virol L Zhang & Y Li 13 Feb 2020
Potential interventions for novel coronavirus in China
Meta analysis of literature showed up
Convalescent Plasma suggested for COV-19 patients.
Cf SARS and MERS 82% homology w COV-19.
Nutritional Intervention:
Vit A, B, C, D, E, ω3-PUFA.
[Insert dietary intervention likely impact on heparan
sulphate biosynthesis a key reverse regulator of NO
and H2S].
Levamisole.
Cyclosporin A.
Gamma Globulin (used during SARS epidemic)
+interferon.
ZINC nanoparticulate antivirals.
Zinc nanoparticles with intrinsic broad spectrum
antiviral activity, cf.
Ghaffani H J Biomed Sci 26 Art No. 70 (2019)

Zinc chelation also inhibits early stges of Dengue virus

replication via NFκB cf. PMID 31632411.

Zinc sulphate + HEPARIN cf PMID 1657829

SILVER nanoparticles cf. PMC 6264685 (also discusses

nanoparticles of other elements, Cu, Zn, Ti, Mg Au
alginate as well as Ag).
Xylan Sulphate E.g. Elmiron

Methylprednisolone (e.g. used together with

thymosin a 1)
Chinese Medicine
Glycrrhyzn (liquorice roots) Baicalin Ginseng
Micro RNA screen PMID 28148804
mR-532-5p : antiviral activity

30/3/20

Taurine and taurine -coupled to small molecules

Can putatively act as an anti-syncytium (a clumping
which lets virus block activities of conventional
immunoglobin -based antiviral effects (as in
conventional vaccines).
Heparin and heparin-like anti-virus agents (may include
pentosan poly-sulphate (e.g. Elmiron or SP54) which
also can potentially be anti-syncytium. (Seen for HIV).

Might be of critical relevance to finding a workable

antiviral for COViD-19.
Also need to look at DMSO for direct antiviral and also
anti-syncytium effect.

Dimethylsulphoxide DMSO originally was thought inert

biologically (so was used as a vehicle for drugs) but was
later found to have a major effect per se on DNA
replication (acting like a mRNA?) and potentially
eliciting potent anti-viral effects.
DMSO was reported in blogs to provide health
benefits. Anti-arthritic. Also apparently pro-health
neurological effects. Can apparently be given e.g. as an
oral drug in conjunction with ascorbate
Reported anecdotal benefit rubbing on skin to get
highly systemic benefit.
Antiviral for herpes. Can greatly (solvent effect)
increase effectiveness of acyclovir action. Allows
better skin penetration. Effect likely to
be more than this however.
Also beneficial for AD. Putative an anti-AD therapy.

30/3/20

Antiviral activities of adamantyl-containing

phosphonous and phosphinic acids Reznikov AN et al.
Russ J Gen Chem 2014 84 1524-30.
Does H2S in mineral (spa) water combat viral infections
of the airways?
Cf. sulphurous mineral water has been found to be of
benefit for airway infections for centuries and is
reported to inhibit chronic obstructive pulmonary
disease (COPD) etc.
(Cf. sites accessed from web survey term “H2S spring
water antiviral”:-
Carbaje JM & Marave F and also later paper by Viegas J
et al f.pubh.2019.00128.
H2S in the correct concentration can be anti-pathogen
including anti-viral (cf e.g. PMID 19659653) but there is
some confusion in the exact situation.

It is of some interest, but scarcely thought elsewhere

to merit comment in the public health scenario that a
gigantic environmental input into the air consists of
vulcanized tyre rubber nanoparticles which retain large
tonnage benzothiazole disulphide vulcanization
accelerator which seems chemically constituted to all a
pro-health slow H2S release in vivo including in the
airways and lungs and if this hypothesis is correct such
pollution may counter the damage to lung tissues
caused by cigarette smoke and other urban air
particulates which putatively are positively correlated
with deaths from viral infections causing pneumonia..
31/3/20

Curcumin (cf PMID 31130924)

Inhibits Influenza A virus
Hepatitis virus, Respiratory Syncytal virus, Dengue virus
Herpes simplex Papilloma
Inhibits HIV (but a curcumin boron complex is
apparently more active).

Green Tea (polyphenols especially epigallocatechin-3-

O-gallate)
demonstrates a similar broad spectrum strong multi-
mechanism antiviral effect to that of curcumin cf, PMID
28805687.
(Influenza, Herpes, HIV, Hepatitis, Ebola, Rotovirus,
etc.)

Tamoxifen
Demonstrates a broad spectrum anti-infectivity
including antiviral activity.
Counters HIV, HCV, HSV, Ebola
Incl. via NFκb.
Prevents activation of RNA polymerase.

(Cf. LC Cham et al Pharmaceuticals 2019 12 142).

Selenium
Aza analogues of Ebselen PMID 15544790 are antiviral,
antimicrobial and antifungal.
Ebselen is also anti-Alzheimers disease (cf PMID
28502066.
Selenoprotein P (antioxidant) interacts with heparan
sulphate (cf. PMID 19345254).
Antiviral diphenyldiselenides PMID 28604620 (2017)
Cf. 14630233.
Selenocysteine + rifampicin PMID 7241092 for
inhibition of influenza A.
Cf. selenazfurin, influenza A and B PMID 3729336
6517540.
Dietary Se etc. influenza etc., cf. PMID 31487871
Se involved centrally in antioxidant defence.
Selenoproteins in ER.
Involved in HIV (may have encoded seleno-protein)
General over Se may encourage viral mutation rate
increase
Selenium dietary supplementation is antiviral e.g.
against Hepatiti B, C pos HIV-1.

POLY-INORGANIC-PHOSPHATE
This (putatively involved-in-early life-and-still-critical-for modern-life e.g. as an
energy source for structuring the extracellular matrix (ECM including heparan
sulphate behaviour) and enabling cognition and memory inter alia) polymer
has been reported (in medium to longer chain forms)
to be anti-viral (for HIV) and also anti-syncytium.
It may become defective in age (cf is reported depleted
in AD; polyPi by removing the most toxic fibrils (the
oligomers by transforming them into less toxic beta
sheet fibrils.
Does this impact on COVID-19 entry to host cells?
Remember that HIV viruses can enter cells via amyloid
fibrils (cf PMID 24832047) generated from prostatic
acid phosphatase and seminogelins
Need to know if this scenario is analogous to the
disease promotion in AD by the more toxic oligomers
from failure of the polyPi protection formed less toxic
beta sheets.
Is failure of polyPi protection part of how highly
infectious viruses enter cells in aged individuals?
It has been recently reported (PMID 30472240) that
polyP 150mer administration protects against
lipopolysaccharide induced septic shock via inhibition
of macrophage recruitment.
And that polyP regulation is a novel therapeutic anti-
septic shock strategy.
Could this help COVID-19 induced septic shock?
The reaction of acetic anhydride with polyPi monomer,
phosphoric acid generates polyPi but the same
reaction with phosphorous acid generates a library of
various interlinked polyethene hydroxide bis-
phosphonates.
Could such bisphosphonates substitute for age- or
pathogen depleted (?) polyPi?

1/4/20
Metformin, possible antiviral effect PMID 29363663
(conceivably could be caused by an increase in H2 S
concentration cf PMID 2390598).
Cf. also Metformin reported on web to Inhibit HIV-1 Dengue Zike Ebola Influenza H1N1).

Thiourea
Non-nucleoside HIV inhibitors PMID 15964195.

Q drain fluid from lungs in COVID-19 crisis?

Cf. cystic fibrosis technique (?)
“How Posture Drainage Can Help” web

A traditional anti-mucus use of ammonium chloride

NH4Cl originally spoken of as ‘ammonchlor’ (an
expectorant) may also be adaptable to COVID-19
therapy?
Could this be of use or perhaps dangerous for
attempted mucus removal from the ling advance lung
congestion by COVID-19?