II.

ANTIVIRAL DRUGS

A. Attachment Antagonists/ Inhibitions of pathogens

Drugs Properties Mode of Action Clinical Considerations Mode of Resistance
β-diketone, a molecule Blocks attachment of Spectrum of action:
containing two ketones molecule on the host cell or picornaviruses, e.g.
Arildone separated by one carbon, pathogen. poliovirus and some cold Unknown
Active against a wide viruses.
variety of DNA and RNA Route: oral
viruses in vitro. Adverse Effect: none
Oseltamivir is a synthetic Prevent influenza viruses Spectrum of action:
derivative prodrug of ethyl from attaching to existing influenza virus
ester with antiviral activity. from cells, it also reduces Route: oral
Oseltamivir blocks viral shedding and Adverse effect: none
Oseltamivir neuraminidases on the infectivity. Unknown
surfaces of influenza
viruses, interfering with
host cell release of
complete viral particles.
Zanamivir is an inhibitor of Prevent influenza viruses Spectrum of action:
the influenza from attaching to existing influenza virus
Zanamivir neuraminidase enzyme and from cells, it also reduces Route: aerosol Unknown
is given by inhalation as viral shedding and Adverse effect: none
therapy and prophylaxis infectivity.
against influenza A and B.
Amantadine is a synthetic Neutralizes acid Spectrum of action: Mutation resulting in a
tricyclic amine with environment within Influenza A virus single amino acid change
antiviral, antiparkinsonian, phagolysosomes that is Route: Oral in a membrane ion channel
Amantadine and anti-hyperalgesia necessary for viral Adverse effect: Toxic to leads to viral resistance.
activities. Amantadine uncoating. central nervous system;
appears to exert its antiviral irritability, insomnia and
effect against the influenza blurred vision.
A virus by interfering with
 the function of the
transmembrane domain of
the viral M2 protein,
thereby preventing the
release of infectious viral
nucleic acids into host
cells.
Rimantadine is a cyclic Neutralizes Spectrum of action: Mutation resulting in a
amine and alpha-methyl phagolysosomes acid and Influenza A virus single amino acid change
derivative preventing viral uncoating Route: Oral in a membrane ion channel
of amantadine with antiviral Adverse effect: Toxic to leads to viral resistance.
activity. Although the exact central nervous system;
mechanism of action of results in nervousness,
rimantadine is not irritability, insomnia and
understood, this agent blurred vision.
Rimantadine appears to exert its antiviral
effect against influenza A
virus by interfering with the
function of the
transmembrane domain of
the viral M2 protein,
thereby preventing the
uncoating of the virus and
subsequent release of
infectious viral nucleic
acids into the cytoplasm of
infected cells
B. Antiviral Drugs that Inhibit Viral Coating
Drugs Properties Mode of Action Clinical Considerations Mode of Resistance
Atazanavir is an antiretroviral Binds to the protease active Spectrum of action: To Reduced binding affinity
protease inhibitor that is used in site and inhibits the activity of treat human between the inhibitor and
the therapy and prevention of the enzyme.  immunodeficiency virus the protease enzyme,
human immunodeficiency virus (HIV) infection. alterations in enzyme
Atazanavir (HIV-1) infection and the acquired Route: Oral catalysis, effects on
immunodeficiency syndrome. Adverse effect: nausea, dimer stability, alterations
jaundice, in inhibitor binding
hyperbilirubinemia, rash, kinetics, and re-shaping
cholestasis, of the active site.
nephrolithiasis.
Darunavir is known to bind to Darunavir selectively blocks Spectrum of action: Individuals experiencing
different sites on the enzyme: the the cleavage of the HIV Gag- inhibits the HIV protease virologic failure while
active site cavity and the surface Pol polyprotein by inhibiting enzyme by forming an using darunavir/ritonavir
of one of the flexible flaps in the the HIV-1 protease enzyme. inhibitor-enzyme 600/100 mg twice daily
protease dimer. Darunavir can This mechanism prevents the complex thereby developed multiple
Darunavir adapt to changes in the shape of maturation of viral particles preventing cleavage of amino acid substitutions
a protease enzyme due to its into infectious virions the gag-pol polyproteins. associated with
molecular flexibility. Route: Oral darunavir resistance as
Adverse effect: listed above (Section A).
headache, diarrhea, However, the V32I
vomiting, stomach pain substitution appeared in
and constipation. more than 30% of
failures 
Fosamprenavir is a prodrug form Fosamprenavir is rapidly Spectrum of action: HIV-1 isolates with
of amprenavir. In the body converted to amprenavir by treatment of human decreased susceptibility
fosamprenavir is metabolized cellular phosphatases in vivo. immunodeficiency virus to amprenavir have been
to amprenavir, a synthetic Amprenavir is an inhibitor of (HIV-1) infection selected in vitro and
derivative of hydroxyethylamine HIV-1 protease. Amprenavir Route: Oral obtained from patients
Fosamprenavir sulfonamide that selectively binds binds to the active site of Adverse effect: nausea, treated with
to and inhibits human HIV-1 protease and thereby fatigue, rash, headache, fosamprenavir.
 immunodeficiency virus (HIV) prevents the processing of diarrhea, vomiting,
protease. viral Gag and Gag-Pol stomach pain and
polyprotein precursors, constipation
resulting in the formation of
immature non-infectious viral
particles.
Saquinavir is a peptide-like Saquinavir is an inhibitor of Spectrum of action: HIV-1 mutants with
substrate analogue that binds to HIV protease. HIV protease binds to the protease reduced susceptibility to
the protease active site and is an enzyme required for the active site and inhibits saquinavir have been
inhibits the activity of the enzyme. proteolytic cleavage of viral the activity of the selected during in vitro
Saquinavir Saquinavir inhibition prevents polyprotein precursors into enzyme. passage. Genotypic
cleavage of the viral polyproteins individual functional proteins Route: Oral analyses of these
resulting in the formation of found in infectious HIV Adverse effect: nausea, isolates showed several
immature noninfectious virus fatigue, rash, headache, substitutions in the HIV
particles. diarrhea, hypoglycemia, protease gene. Only the
stomach pain, abdominal G48V and L90M
discomfort, buccal substitutions were
mucosa ulceration, associated with reduced
paresthesia. susceptibility to
saquinavir, and
conferred an increase in
the IC50 value of 8- and
3-fold, respectively.
Ritonavir is an L-valine derivative Ritonavir inhibits the HIV viral Spectrum of action: Reduced binding affinity
that is L-valinamide in which proteinase enzyme that binds to the protease between the inhibitor and
alpha-amino group has been normally cleaves the active site and inhibits the protease enzyme,
acylated by a [(2-isopropyl-1,3- structural and replicative the activity of the alterations in enzyme
thiazol-4-yl)methyl]methyl proteins that arise from major enzyme. catalysis, effects on
carbamoyl group and in which HIV genes, such Route: Oral dimer stability, alterations
Ritonavir a hydrogen of the as gag and pol. Gag encode Adverse effect: in inhibitor binding
carboxamide amino group has s proteins involved in the hyperglycemia, kinetics, and re-shaping
been replaced by a (2R,4S,5S)-4- core and the nucleocapsid, pancreatitis, nausea, of the active site.
hydroxy-1,6-diphenyl-5-{[(1,3- while pol encodes the HIV fatigue, rash, headache,
thiazol-5- reverse transcriptase, diarrhea, hypoglycemia,
ylmethoxy)carbonyl]amino}hexan ribonuclease H, integrase, stomach pain, abdominal
-2-yl group. and protease. discomfort, buccal
mucosa ulceration,
paresthesia.
C. Antiviral Drugs that Inhibit Nucleic Acid Synthesis Acyclovir (ACV)
Drugs Properties Mode of Action Clinical Considerations Mode of Resistance
Acyclovir is a nucleoside Phosphorylation by virally Spectrum of action: Viruses Mutation in genes for
analogue and antiviral coded kinase enzyme that code for kinase kinase enzymes may
agent used in therapy of activates the drug: Inhibits enzymes, herpes, Epstein- render them ineffective at
Acyclovir herpes and varicella-zoster DNA and RNA synthesis. bar virus, cytomegalovirus, drug activation
virus infections. and varicella virus
Route: Oral
Adverse effects: none

Vidarabine Anhydrous is an Phosphorylation by cell- Spectrum of action: Results from mutation of

anhydrous form of
vidarabine, a nucleoside
analog with activity against
herpes simplex virus and
Adenosine Arabinoside varicella zoster virus.
Vidarabine is converted to
a monophosphate by
viral thymidine kinase and
is further modified to
a triphosphate form by host
enzymes
Ribavirin is a nucleoside
analogue and antiviral
agent used in therapy of
chronic hepatitis C and
Ribavirin other flavivirus infections.
coded kinase enzyme Herpesvirus viral DNA polymerase
activates the drug; inhibits Route: IV
DNA synthesis; viral DNA Adverse effects: Fatal to
polymerase ore likely to host cells that incorporate
incorporate the drugs than the drug into cellular DNA;
huma DNA polymerase anemia
Phosphorylation by virally Spectrum of action:
coded kinase enzymes Respiratory syncytial,
activates drug; inhibits DNA hepatitis C, influenza A,
and RNA synthesis; viral measles, some
DNA polymerase more hemorrhagic fever viruses Unknown
likely to incorporate the Route: IV, Oral, Aerosol
drugs. Adverse effects: perhaps
harmful to developing fetus

Valacyclovir is the Phosphorylation by cell- Spectrum of action: HIV, Results from mutation of
hydrochloride salt of the L- coded kinase enzyme hepatitis B virus viral reverse transcriptase
 valyl ester of the antiviral activates the drug; inhibits Route: Oral
drug acyclovir. Orally DNA synthesis; viral Adverse effects: nausea,
administered, valacyclovir reverse transcriptase more bone marrow toxicity
is rapidly converted likely to incorporate these
to acyclovir which inhibits drugs; used in conjunction
Valacidovir viral DNA replication after with the protease inhibitor
further conversion to the to treat HIV
nucleotide analog acyclovir
triphosphate by
viral thymidine kinase,
cellular guanyl cyclase, and
a number of other cellular
enzymes
Adefovir is a member of the Phosphorylation by cell- Spectrum of action: HIV, Results from mutation of
class of phosphonic acids coded kinase enzyme hepatitis B virus viral reverse transcriptase
that is methylphosphonic activates the drug; inhibits Route: Oral
acid in which one of the DNA synthesis; viral Adverse effects: nausea,
methyl hydrogens has been reverse transcriptase more bone marrow toxicity
replaced by a 2-(6-amino- likely to incorporate these
9H-purin-9-yl)ethoxy group. drugs; used in conjunction
An inhibitor of HIV-1 with the protease inhibitor
Adefovir reverse transcriptase, the to treat HIV
bis(t-
butoxycarbonyloxymethyl)
ester (dipivoxil ester)
prodrug is used to treat
chronic hepatitis B viral
infection.

D. Antiviral Drugs that Inhibit Viral Proteins

Drugs Properties Mode of Action Clinical Considerations Mode of Resistance
 Indinavir is a N-(2- The medication binds the Spectrum of action: HIV Results from mutation in
hydroxyethyl)piperazine, active catalytic site of HIV and Hepatitis C virus protease gene
a piperazine protease, inhibiting the Route: oral
Indinavir carboxamide and a enzyme's ability to cleave Adverse effects: none
dicarboxylic acid diamide. It polypeptides into active,
has a role as a HIV infectious proteins.
protease inhibitor.
Nelfinavir is an aryl sulfide Nelfinavir binds to the Spectrum of action: HIV Results from mutation in
that is used (as its protease active site and and Hepatitis C virus protease gene
mesylate salt) for treatment inhibits the activity of the Route: oral
of HIV and also exhibits enzyme. Adverse effects: none
some anticancer
properties. It has a role as
Nelfinavir a HIV protease inhibitor
and an antineoplastic
agent. It is a member of
benzamides, a member of
phenols, an aryl sulfide, a
secondary alcohol, a
tertiary amino compound
and an organic
heterobicyclic compound.
Amprenavir is a Amprenavir binds to the Spectrum of action: HIV Results from mutation in
tetrahydrofuryl ester, a protease active site and and Hepatitis C virus protease gene
sulfonamide and a inhibits the activity of the Route: oral
Amprenavir carbamate ester. It has a enzyme Adverse effects: none
role as a HIV protease
inhibitor and an antiviral
drug.
Lopinavir is a dicarboxylic Ritonavir inhibits the HIV viral Spectrum of action:  binds Reduced binding affinity
acid diamide that proteinase enzyme that to the protease active site between the inhibitor and
is amphetamine is normally cleaves the and inhibits the activity of the protease enzyme,
substituted on nitrogen by structural and replicative the enzyme. alterations in enzyme
 Lopinavir a (2,6-
dimethylphenoxy)acetyl
group and on
the carbon alpha-
to nitrogen by a (1S,3S)-1-
hydroxy-3-{[(2S)-3-methyl-
2-(2-
oxotetrahydropyrimidin-1-
yl)butanoyl]amino}-4-
phenylbutyl group.
Telaprevir is an orally
available peptidomimetic
small molecule with activity
against hepatitis C virus
(HCV). Telaprivir is a
selective protease inhibitor
that targets the viral HCV
Telaprevir NS3-4A serine protease
and disrupts processing of
viral proteins and formation
of a viral replication
complex.
III. ANTIFUNGAL DRUGS
A. Antifungal Drugs that Inhibit Cell Membrane
proteins that arise from major Route: Oral catalysis, effects on dimer
HIV genes, such Adverse effect: stability, alterations in
as gag and pol. Gag encode hyperglycemia, inhibitor binding kinetics,
s proteins involved in the pancreatitis, nausea, and re-shaping of the
core and the nucleocapsid, fatigue, rash, headache, active site.
while pol encodes the HIV diarrhea, hypoglycemia,
reverse transcriptase, stomach pain, abdominal
ribonuclease H, integrase, discomfort, buccal mucosa
and protease. ulceration, paresthesia.
Computer assisted modeling Spectrum of action: HIV Results from mutation in
of protease enzymes, which and Hepatitis C virus protease gene
are unique to HIV and Route: oral
hepatitis c virus, allowed the Adverse effects: none
creation of drugs that block
the enzymes active sites,
often used in conjunction
with dugs active against
nucleic acid synthesis
 Drugs Properties Mode of Action Clinical Considerations Mode of Resistance
Allylamines act by inhibiting Antifungal action due to Spectrum of action: fungi
early steps of ergosterol inhibition of ergosterol Route: Oral, IV
Allylamines biosynthesis synthesis Adverse effects: headache, Unknown
nausea, vomiting, diarrhea,
rash and liver damage

Azole-derived compounds Antifungal action due to Spectrum of action: Fungi Mutation gene for target
are widely used as inhibition of synthesis of and protozoa enzyme.
antifungal agents due to ergosterol, an essential Route: topical, IV
their properties like broad component of fungal Adverse effects: possibly
Azoles spectrum of action, chemical cytoplasmic membranes. causes cancer in humas
stability, and oral
bioavailability. The activity of
azoles against fungi is
based on the inhibition of
ergosterol
Contains a mecloxamine Associate with molecules Spectrum of action: Fungi Rare; decrease in amount
moiety linked to the macro of ergosterol, forming a some amoeba or charge in chemistry
lactone ring via a β- pore through the fungal Route: Amphotericin B, IV, ergosterol.
glycosidic bond, membrane, which leads to nystatin, topical
Polyenes leakage of essential ions Adverse effects: Chills
from the cell; amphotericin vomiting, fever
B is produced by
Streptomyces nodosus
Ciclopirox is a cyclic Synthetic antimetabolite Spectrum of action: Fungi Unknown
hydroxamic acid that is 1- that appears to disrupt especially Trichophyton
Ciclopirox hydroxypyridin-2(1H)-one in DNA repair, inhibit mitosis, Route: Topical
which the hydrogens at and interfere with some Adverse effects: Possible
positions 4 and 6 are aspects of intracellular burning sensation at
substituted by methyl and transport application site
cyclohexyl groups,
respectively. A broad
 spectrum antigfungal agent,
it also exhibits antibacterial
activity against many Gram-
positive and Gram-negative
bacteria, and has anti-
inflammatory properties. It is
used a a topical treatment of
fungal skin and nail
infections. It has a role as an
antibacterial agent and an
antiseborrheic. It is
a pyridone, a cyclic
hydroxamic acid and
a hydroxypyridone antifunga
l drug.
 It is used for the treatment Inhibits synthesis of glucan Spectrum of action: Results from mutation in
of invasive candidiasis, subunit of fungal cell walls Candida, aspergillus glucan synthase gene
especially in critically ill and Route: IV
Echinocandins neutropenic patients Adverse effects: rash,
facial swelling, respiratory
spasms, gi distress, toxic
to human embryos

IV. ANTIHELMINTHIC DRUGS

Drugs Properties Mode of Action Clinical Considerations Mode of Resistance

Albendazole is a broad- Inhibit microtubule Spectrum of action:
 spectrum, formation and glucose Helminth, protozoa
synthetic benzimidazole- uptake Route: Oral
derivative anthelmintic. Adverse effects: possible
Albendazole interferes with diarrhea
the reproduction and
Albendazole survival of helminths by Unknown
inhibiting the formation of
microtubules from tubulin.
This leads to an impaired
uptake of glucose, a
depletion
of glycogen stores, and
results in the worm's
death. 
Diiodohydroxyquinoline, Halogenated (iodine Spectrum of action:
also known as uidoquinol containing) works by Entamoeba
and iodoquinol, is sequestering iron ions Route: Oral Unknown
Iodoquinol a quinoline derivative that required by protozoan Adverse effects:
can be used in the Neuropathy and blindness
treatment of amoebiasis with prolonged use

Produce flaccid paralysis Spectrum of action:

by blocking Helminths
neurotransmitters Route: Oral
Ivermectin Metrifonate Unkwon Adverse effects: allergic Unknown
reactions may result from
antigens of dead helminths

Niclosamide is a secondary Inhibits oxidative Spectrum of action:

carboxamide resulting from phosphorylation of ATP by Cestodes
the formal condensation of mitochondria Route: oral
the carboxy group of 5- Adverse effects: Abdominal
chlorosalicylic acid with pain, nausea and diarrhea
 the amino group of 2-
chloro-4-nitroaniline. It is an
oral anthelmintic drug
approved for use against
tapeworm infections. It has
a role as a piscicide, a
molluscicide, an
antiparasitic agent, an
Niclosamide anticoronaviral agent, an Unknown
anthelminthic drug, an
apoptosis inducer and a
STAT3 inhibitor. It is a
member of
monochlorobenzenes, a
member of salicylanilides, a
C-nitro compound, a
secondary carboxamide
and a member of
benzamides. It is
functionally related to a 5-
chlorosalicylic acid.
Praziquantel is an Changes membrane Spectrum of action:
anthelmintic agent with permeability receptors, cestodes, trematodes
activity against a broad causing complete muscular Route: Oral
Praziquantel spectrum of trematodes contraction of helminths Adverse effects: None Unknown
and cestodes that is used
predominantly in the
therapy of schistosomiasis,
liver flukes, and
cysticercosis.