Part-3: Anti-viral Agents

These are the agents which are used in prophylaxis and treatment of viral infections (diseases caused
by viruses).

Viral diseases: Influenza, rabies, yellow fever, poliomyelitis, mumps, measles, HIV, small pox

Structure of Virus:

 Smaller in size & can be seen by ultramicroscope or electron microscope

 Obligate parasites as they replicate only within host cell & replication depends on host metabolic
processes
 simple chemical composition: No cell wall but have RNA or DNA (only one) enclosed in a shell
of protein called capsid. The capsid is composed of several subunits called capsomers & rarely
covered with lipid layer.

DNA virus: Eg: Herpes virus, Pox virus

RNA virus: Eg: Retroviruses:

 Responsible for AIDS (Acquired Immuno-deficiency syndrome) & T-leukaemia

 Contain reverse transcriptase enzyme activity that makes DNA copy from viral RNA template.
This DNA is then inserted in host genome (provirus) & is transcribed into genomic RNA and
mRNA for translocation into viral proteins, making new viral particles.

Viral life cycle

1. Adsorption: Attachment of virus to host cell

2. Penetration: Penetration of virus into host cell
3. Uncoating: Genetic material (DNA or RNA) passes into host cell leaving capsid covering outside
host cell
4. Biosynthesis:
Transcription: Production of viral mRNA from viral genome
Translation: Viral genome enters cytoplasm or nucleoplasm and directs host machinery for
synthesis of new viral particles. Viral particles modify host cell and allows viral genome to
replicate by using host and viral enzyme. It happens when cell is irreversibly modified & then
eventually be killed. Since host cell machinery is totally utilized by virus, normal cell function is
affected.
5. Assembly of viral particles: New viral coat protein assembles into capsid & viral genome.
6. Release of new virus: Release of virus from cell occurs through budding process or rupture. It
repeats in new host cell.

Antiviral agents act at various stages like attachment, replication & release of virus.
I. Adamantane Amines

Drug R MOA Uses

Amantadine NH2 Inhibit uncoating of viral RNA of Influenza type-A
Rimantadine CH(CH3)-NH2 Influenza type-A virus Parkinson’s disease
SAR of Adamantane Amines:

 R=NH2  Amantadine
 R= -CH(CH3)-NH2  Rimantadine
 N-alkyl or N, N-dialkyl derivatives exhibit antiviral activity equal to adamantine.
 N-acyl derivatives show decreased activity.
 Replacement of –NH2 with OH, SH, CN, halogen  Inactive
 Optical isomers and racemic mixtures are equally active.

II. Reverse Transcriptase Inhibitors:

1. Purine nucleosides & nucleotides:

Drug R1 R2 MOA Uses

Acyclovir NH2 CH2OCH2CH2OH Reverse Transcriptase Herpes simplex,
Ganciclovir NH2 CH2OCH(CH2OH)2 inhibitors & hence Chickenpox
Didanosine H inhibits viral replication caused by
(formation of viral Varicella zoster
DNA from viral RNA) virus
& stops synthesis of
further viral particle.

MOA of Acyclovir:

2. Pyrimidine nucleosides & nucleotides

 Drug X R1 R2 R3 R4 MOA Uses
Idoxuridine C =O I H OH Herpes simplex
Reverse Transcriptase
Zidovudine/ C =O CH3 H N3
inhibitors & hence inhibits
Azido- Advance HIV
viral replication (formation of
deoxythymidine infections, AIDS
viral DNA from viral RNA) &
(AZT) & AIDS-related
stops synthesis of further viral
Lamivudine S NH2 H H - complex (ARC)
particle.
Zalcitabine C NH2 H H H
Synthesis of Acyclovir

3. Non-nucleoside RT inhibitors

Loviride Delavirdine

III. HIV Protease Inhibitors: Saquinavir, Indinavir, Ritonavir

IV. Miscellaneous

Ribavirin