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ANTIVIRAL AGENTS

Moses Masika; MBChB, MSc
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Adverse effect
Cure vs Treatment

Viral Characteristics
Intracellular life
No organelles
Require specific receptors to attach (viral tropism)
Exploit host enzymes for replication
Virus-specific targets do exist
High level of mutation

Classification of Antiviral Agents
By mechanism of action
By target condition
By mode of administration
By chemical composition

Classification by Target virus
1
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Anti-influenza agents
Uncoating Inhibitors
Amantadine
Rimantadine

Viral release inhibitors
Oseltamivir
Zanamivir

3
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Anti-Hepatitis C virus agents
Immunomodulant
Interferon
RNA Polymerase Inhibitors
Ribavirin
Sofosbuvir
Protease Inhibitors
Bocepravir
Telaprevir
Simeprevir

5
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g
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)
Viral Assembly
Viral release

Source: Katzung – Basic & Clinical Pharmacology 11th Edition © The McGraw Hill Companies Inc
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Receptor binding Inhibitors
Maraviroc
Blocks CCR5 co-receptor preventing binding of HIV gp120
in M5 – tropic HIV
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Fusion inhibitors
Enfuvirtide
Blocks conformational change of HIV gp41 hence preventing
fusion with host cell membrane

Palivizumab
A monoclonal antibody that binds F protein of RSV
preventing fusion

Docosanol (cream)
Prevents fusion of HSV with host cell mebrane

3
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Nucleic acid synthesis inhibitors
A
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DNA Integration inhibitors
C
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Nucleoside analogues
Acyclovir, Trifluridine, Idoxuridine
ii
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Pyrophosphate analogues:
Foscarnet, Phosphonoacetic acid

Idoxyuridine
First licensed antiviral agent (1963)
A pyrimidine analogue
Inhibits viral DNA polymerase
Non-selective – also inhibits host DNA polymerase
Occasionally used topically (Herpetic keratitis)
Largely replaced by less toxic drugs e
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Acyclovir

Acyclovir
Acyclic guanosine (nucleoside) analogue
Active against HSV-1, HSV-2 and VZV (VZV requires higher dose)
Weak in-vitro activity against EBV, CMV & HHV-6
A pro-drug, undergoes 3 phosphorylation steps to its active form
Initial phosphorylation by Viral-specific thymidine kinase
(This makes it selective for virus-infected cells)
Subsequent di & tri phosphorylation by host-cell enzymes

Acyclovir…
MoA: Tri-phosphorylated acyclovir competes with
endogenous nucleotide (deoxyGTP) for DNA Polymerase
and causes chain termination once incorporated
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Trifluridine
2
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Foscarnet

Reverse Transcriptase Inhibitors
Block DNA synthesis from RNA by Reverse transcriptase
aka RNA-dependent DNA polymerase
i
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Nucleotide RT Inhibitors (NtRTIs)
Tenofovir, Adefovir

iii
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DNA Integration inhibitors
Prevent integration of viral DNA into host
genome by binding Integrase
Raltegravir
Dolutegravir
Both are ARVs

4(c)
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Protein Synthesis Inhibitors
Formivirsen

5'-GCG TTT GCT CTT CTT CTT GCG-3'

An anti-sense oligonucleotide that binds the
complementary mRNA preventing translation into
protein
Stabilized by phosphorothioate to prevent
degradation by nucleases
Used to treat CMV retinitis – intravitreal injection

6
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Viral release inhibitors
Oseltamivir
Zanamivir
Block viral neuraminidase of Influenza A & B
Sialic acid is the influenza virus receptor
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Interferons
Potent cytokines with antiviral, immunomodulatory and
antiproliferative activity
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Receptor binding inhibitors
2
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Uncoating inhibitors
4
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Protein synthesis inhibitors
6
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Viral release inhibitors
8
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University of South Carolina
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Microbiology and immunology online University of South Carolina School of Medicine
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microbiologybook
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htm

2
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Brunton, Chabner & Knollman - Goodman and Gilman's The Pharmacological
Basis of Therapeutics, 12th Edition

4
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, Mishra, N
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(2009)
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5
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, Gowen, B
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, Takahashi, K
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, Smee, D
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, & Barnard, D
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(2013)
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Antiviral
Res, 100(2), 446-454
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1016/j
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2013
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015



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