Transcript Antiviral Drugs Part 2

Inhibitors of Other Viruses
A.
RIBAVIRIN
Ribavirin (Virazole) is a nucleoside analogue in
which a triazolecarboxamide moiety is substituted
on place of the normal purine precursor
aminoimidazolecarboxamide
** The drug inhibits the synthesis
of guanine nucleotides, which
are essential for both DNA
and RNA viruses.
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- Ribavirin aerosol is used clinically to treat pneumonitis
caused by respiratory syncytial virus in infants and to
treat severe influenza B infections.
B. ADEFOVIR
Adefovir (Hepsera) is a nucleotide analogue of
adenosine monophosphate that inhibits the DNA
polymerase of hepatitis B virus. It is used for the
treatment of chronic active hepatitis caused by
this virus.
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C. Entecavir
Entecavir ( baraclude ) is guanosine
analogue that inhibits the DNA polymerase
of hepatitis B virus (HBV) .
 It has no activity against the DNA
( reverse transcriptase ) of HIV.
 Its approved for the treatment of adults
with chronic HBV infection .

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INHIBITION OF CLEAVAGE
OF PRECURSOR POLYPEPTIDES
Several drugs, such as saquinavir (Invirase,
Fortovase), indinavir (Crixivan), ritonavir (Norvir),
amprenavir (Agenerase), and nelfinavir (Viracept),
are inhibitors of the protease encoded by HIV .
These inhibitors contain peptide bonds that bind to the
active site of the viral protease, thereby preventing
the protease from cleaving the viral precursor.
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
These drugs inhibit production of
infectious virions but do not affect the
proviral DNA and therefore do not cure
the infection. The effect of protease
inhibitors on the replication of HIV is
depicted in the next Figure
- Virion: A complete virus particle with its DNA or RNA core and protein
coat as it exists outside the cell. Also called a viral particle.
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
Monotherapy with protease inhibitors
should not be used because resistant
mutants emerge rapidly.

These drugs are prescribed in combination
with reverse transcriptase inhibitors, either
nucleoside analogues such as zidovudine
and lamivudine or non-nucleoside
inhibitors such as nevirapine.
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The side effects of protease inhibitors
include nausea, diarrhea, and abnormal
fat accumulation in the back of the neck
that can result in a "buffalo hump"
appearance.
The metabolic process by which this
occurs is unknown.
- Indinavir can cause kidney stones; thus,
extra water should be consumed to reduce
the likelihood of stone formation.
- Ritonavir can cause circumoral
paresthesias.

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INHIBITION OF VIRAL PROTEIN
SYNTHESIS
A.
INTERFERON
The mode of action of interferon is discussed in Chapter 33
with dr. Ali Shaaban
Recombinant alpha interferon is effective in the
treatment of some patients with chronic
hepatitis B and chronic hepatitis C infections.
It also causes regression of condylomata
acuminata lesions caused by human
papillomavirus and the lesions of Kaposi's
sarcoma caused by human herpesvirus-8.
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
Pegylated interferon (Peg-intron), which is
interferon alpha conjugated to
polyethylene glycol, is available for the
treatment of chronic hepatitis C.
B. FOMIVIRSEN
Fomivirsen (Vitravene) is an andsense DNA
that blocks the replication of CMV.
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- Antisense DNA is a single-stranded DNA
whose base sequence is the complement
of the viral mRNA.
- Antisense DNA binds to the mRNA within
the infected cell and prevents it from being
translated into viral protein.
- Fomivirsen is approved for the intraocular
treatment of CMV retinitis. It is the first
and, at present, the only antisense
molecule to be approved for the treatment
of human disease.
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C. METHISAZONE
Methisazone
 (N-methylisatin-β-thiosemicarbazone)
specifically inhibits the protein synthesis of
poxviruses, such as smallpox and vaccinia
viruses, by blocking the translation of late
mRNA.

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INHIBITION OF RELEASE OF VIRUS
Zanamivir (Relenza) and oseltamivir
(Tamiflu) inhibit the neuraminidase of
influenza virus. This enzyme is located on
the surface of influenza virus and is
required for the release of the virus from
infected cells.
 Inhibition of release of influenza virus
limits the infection by reducing the spread
of virus from one cell to another.

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
These drugs are effective against both
influenza A and B viruses, in contrast to
amantadine, which is effective only against
influenza A virus.

These drugs are effective against strains
of influenza virus resistant to amantadine.
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CHEMOPROPHYLAXlS

In most instances, the antiviral agents
described in this chapter are used to treat
infectious diseases. However, there are
times when they are used to prevent
diseases from occurring, a process called
chemoprophylaxis. Table 35-2 describes
the drugs used for this purpose
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