ANTIVIRAL CHEMOTHERAPEUTIC DRUGS

Viruses are intracellular obligate parasites; their replication depends on the host cell synthesis
process. Viruses are host specific.
Viral replication consists of;
a. Adsorption to and penetration into susceptible host cells.
b. Uncoating of viral nucleic acid.
c. Synthesis of early regulatory proteins e.g. Nucleic acid polymerase.
d. Synthesis of DNA/RNA and not both.
e. Synthesis of late structural proteins.
f. Assembly (maturation) of viral particles.
g. Finally release from the cell.
The antiviral drugs/agent can target any of the replication steps.
Most of the drugs currently available act on the synthesis of purines and pyrimidines in step (d);
reverse transcriptase inhibitors block transcription of the HIV RNA genome into DNA, thereby
preventing the synthesis of viral m RNA and protein.
The protease inhibitors act on the synthesis of late proteins and packaging.
Antiviral drugs used in the treatment of herpes, HIV and others are discussed below;

ANTIHERPS AGENTS.
(a) Acyclovir
Acyclovir Triphosphate inhibits viral DNA synthesis by two mechanism;
(a) Competitive inhibition of the viral DNA Polymerase.
(b) By binding to the DNA template as an irreversible complex.
Acyclovir is available in;
Oral Acyclovir which is effective for treatment of primary infections and recurrence of genital
and labia herpes
Intravenous Acyclovir which is effective treatment of choice for Herpes simplex, Neonatal HSV
and severe primary recurrent.
Acyclovir diffuses into most tissues and body fluid to produce concentrations that are 50-100%
of those in serum.
 Adverse reaction: it is well tolerated. Nausea, diarrhea and headache have occasionally been
reported.
(b)Ganciclovir
The activated compound competitively inhibits viral DNA Polymerase causing an unstable
compound but does not result to chai termination.
Has activity against CMV, HSV, VZV and EBV.
Its activity against CMV is 100 times greater than that of Acyclovir.
Clinical Use: IV Ganciclovir is indicated in treatment of CMV retinitis in patients with AIDS. It
also reduces incidences of symptomatic CMV disease if administered before organ
transplantation. Also treat CMV colitis and esophagitis.
Adverse reactions: central nervous system toxicity and myelosuppression neutropenia.
(c) Idoxirudine
A substituted pyramidine analog was the first antiviral agent to be approved.
It is used tropically on herpes keratitis because of its lack of selectivity it is too toxic for
systemic administration.
(d) Vidarabine
As a 3% ointment is effective treatment for acute keratoconjuctvitis, superficial keratitis
and recurrent epithelial keratitis due to HSV.
It is eliminated by renal mechanism as the hypoxathine.

ANTIRETROVIRAL AGENTS

Are synthetic agents that have antiviral activity against HIV and are used in their
management.
Are of four different classes: Nucleoside reverse transcriptase inhibitors (NRTI), Protease
inhibitor, Nonnucleoside reverse transcriptase inhibitors (NNRTI) and Fusion inhibitors.

 Fusion inhibitors
Enfuvirtide(T-20) is the first approved agent in fusion inhibitors. Can be prescribed with
other antiretrovirals. Has a robust safety profile.
 Protease Inhibitors
(a)Indinavir
Is a specific inhibitor of HIV-1 protease, an enzyme responsible for mature infectious
virons. It is recommended to use with reverse transcriptase .
 (b) Ritonavir
A inhibitor of HIV-1 with a high bioavailabilty . common adverse effects are
gastrointestinal disturbance .
© Saquinivir
Is a synthetic peptide like substance analog that inhibits the activity of HIV 1 protease and
prevents cleavage of viral polyproteins.

 RTI
Limuvudine
Nucleoside analog in the vitro against HIV-1. Inhibits transcriptase of HIV-1. it is
administered in combination with zudovudine or another analog. Effects are headaches,
fatigue ,insomnia
Zidovudine
It requires anabolic phosphorylation for activation to form 5-triphospahte
Enters the cell by passive diffusion and phosphorylated via cellular kinase
Triphosphate is a competitive inhibitor of deoxithymide triphosphate for reverse
transcriptase. Additionally, it acts as a chain of terminator in the proviral DNA synthesis.
Adverse effects are headache, insomnia, gastrointestinal intolerance.

Other antiviral inhibitors are Amantadine and Rimantadine