Baedah Madjid DEPART.

OF MICROBIOLOGY, MEDICAL FACULTY, HASANUDIN UNIVERSITY 2007

 Number of drugs available: limited

Difficult to obtain selective toxicity to virus: replication of virus is the normal synthetic process of the cell Several virus-specific replication steps the site of action of effective antiviral drugs. Antiviral drugs are relatively ineffective: many cycle of viral replication occur during the incubation time. Some viruses become latent within the cell: no current antiviral drugs can eradicate them. Emergence of drug resistance viral mutans.

 Inhibition of Viral Nucleic Acid Synthesis Inhibition of Cleavage of Precursor Polypetides Inhibition of Viral Protein Synthesis Inhibition of Release of Virus

Antiviral agents used to treat infectious

diseases Some times they are used to prevent

diseases: chemoprophylaxis

Inhibitor of Herpesviruses
A. Nucleoside Inhibitors: inhibit the DNA polymerase of
one or more members of the herpesvirus family. 1. Acyclovir: a guanosine analougue thathas three-carbon
fragment in place of ribose.

2. Ganciclovir : a nucleoside analogue of guanine 3. Cidofovir: a nucleoside analogue of cytosine

4. Vidarabine: a nucleoside analogue with arabinose in a

place of ribose

5. Iododeoxyuridine: a nucleoside analogue in which the

metghyl group of thymine is replaced by an iodine atom. 6. Trifluorothymidine: a nucleoside analogue in which the metghyl group of thymine contains 3 fluorine atoms instead of 3 hydrogen atoms

B. Non-Nucleoside Inhibitors: inhibit polymerase of herpesviruses

by mechanisms distinct from the nucleoside analogoes discribe above. 1. Foscarnet: a pyrophosphate analogue.

Inhibitor of Retroviruses
A. Nucleoside Inhibitors
Inhibit the DNA synthesis by the reverse transcriptase of HIV

1. Azidothymidine: a nucleoside analogue that causes chain

2. Dideoxyinosine: a nucleoside analogue that causes chain

termination during DNA synthesis: it has an acido-group in place of th hydroxyl group on the ribose.
termination during DNA synthesis: it is missing hydroxyl group on the ribose.

3. Dideoxycytidine: a nucleoside analogue that causes chain

termination during DNA synthesis: it is missing hydroxyl group on the ribose.

Inhibitor of Retroviruses A.Nucleoside Inhibitors

4. Stavudine: a nucleoside analogue that causes chain
termination during DNA synthesis by the reverse transcriptase of HIV

5. Lamivudine: a nucleoside analogue that causes chain

termination during DNA synthesis by the reverse transcriptase of HIV 6. Abacavir: a nucleoside analogue that causes chain termination during DNA synthesis 7. Tenovovir: an acyclic nucleoside: an analogous of adenosine monophosphate reverse transcriptase inhibitor that act by chain termination.

Inhibitor of Retroviruses
B. Non-Nucleoside Inhibitor: not nucleoside analogue & do
not cause chain termination. The non-nucleoside termination reverse transcriptase inhibitors (NNRTI).

1. Nevirapine: usually used in combination with zidovidine &

didanosine. Side effect: skin rash.

2. Delavirdine: effective in combination with either zidovudine

or zidovudine plus didanosine.

3. Efavirenz: in combination with zidovudine plus lamivudine

was more effective and better tolerated than the combination of indinavir, zidovudine, and lamivudine. The most common side effects: dizziness, insomnia and headaches.

Inhibitor to Other Viruses

1. Ribavirin: a nucleoside analogue in which a triazolecarboxamide is substituted in place of the normal purine precursor aminoimidazole-carboxamide. The drug inhibit the synthesis of guanine nucleotides, which is essential for both DNA and RNA viruses.

2. Adefovir: a nucleotide analogue of adenosine monophosphate

that inhibits the DNA polymerase of hepatitis B virus. It is used for treatment of chronic active hepatitis cause by this virus.

3. Entecavir: a guanosine analogue that inhibits the DNA

polymerase of hepatitis B virus. It has no activity againts the DNA polymerase (reverse transcriptase) of HIV.

It is approved for treatment of adults with chronic HBV infection.

Inhibits the protease encoded by HIV

Saqunair, indinavir, ritonavir, amprenavir, & nevinavir.
The drugs inhibit production of infectious virion but do not affect the proviral DNA do not cure the infections. Monotherapy with protease inhibitors should not be used because resistance mutants emerge rapidly. This drugs are used in combination with a reverse transcriptase inhibitors, either nucleoside analogues or nonnucleoside inhibitors. The side effects: nausea, diarrhea, and abnormal fat accumulation in the back of the neck that can result in a buffalo hump appearance.

A. Interferon:
a heterogenous group of glvcoproteins produced by human and other animal cells after viral infection. mode of action: inhibits the growth of virus by blocking the translation of viral protein.

recombinant alpha interferon is effective in the treatment of chronic hepatitis B & chronic hepatitis C patients.

B. Formivirsin:
an antisense DNA that block the replication of CMV.

an antisense DNA: single-stranded DNA whose base sequence is the complement of the viral mRNA.

C. Methiazone:
specifically inhibits the protein synthesis of poxviruses, by blocking the translation of late mRNA.. rarely used because the smallpox vaccine is no longer administrated.

Zanamivir & Oseltamivir

Inhibits the neuraminidase of influenza virus The enzym is located on the surface of influenza virus and is required for the release of the virus

from the infected cells. Inhibition of the virus release limits the infection by reducing the spread of virus from one cell to another. Effective against both influenza A and B viruses, in contras to amantadine, which is effective only against influenza A virus.

DRUGS
Amantadine

USE
Prevention of influenza during outbreaks caused by influenza A virus.

Acyclovir
Ganciclovir Azidothymine or Nevirapine

Prevention of disseminated HSV or VZV disease in immunocompromised patients.

Prevention of disseminated CMV disease in immunocompromised, especially retinitis in AIDS patients. Prevention of HIV infection in neonate

Azidothymidine, Lamivudine, & Indinavir

Prevention of HIV infection in needle-stick injuries.