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

2. Dideoxyinosine: a nucleoside analogue that causes chain

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 triazole-
carboxamide 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 non-
nucleoside 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 USE
Amantadine Prevention of influenza during outbreaks
caused by influenza A virus.
Acyclovir Prevention of disseminated HSV or VZV
disease in immunocompromised patients.
Ganciclovir Prevention of disseminated CMV disease in
immunocompromised, especially retinitis in
AIDS patients.
Azidothymine or Prevention of HIV infection in neonate
Nevirapine
Azidothymidine, Prevention of HIV infection in needle-stick
Lamivudine, & injuries.
Indinavir