5. Anti-herpes drugs
Acyclovir is a guanosine analog active against herpes
simplex virus (HSV-1, HSV-2) and varicella-zoster virus
(VZV). The drug is activated to form acyclovir
triphosphate, which interferes with viral synthesis in 2
ways. It acts as a competitive substrate for DNA
polymerase, and it leads to chain termination after its
incorporation into viral DNA.
Resistance of HSV can involve changes in viral DNA
polymerase. However, many resistant strains of HSV
(TK–
strains) lack thymidine kinase, the enzyme involved
in the initial viral-specific phosphorylation of acyclovir.
Such strains are cross-resistant to famciclovir,
ganciclovir, and valacyclovir.
7. Anti HIV drugs
The primary drugs effective against HIV are antimetabolite
inhibitors of viral reverse transcriptase and inhibitors of viral
aspartate protease.
The current approach to treatment of infection with HIV is the
initiation of treatment with 3 or more antiretroviral drugs, if
possible, before symptoms appear.
Such combinations usually include nucleoside reverse
transcriptase inhibitors (NRTIs) together with inhibitors of
HIV protease (PI). Highly active antiretroviral therapy
(HAART) involving drug combinations can slow or reverse the
increases in viral RNA load that normally accompany
progression of disease. In many AIDS patients, HAART slows
or reverses the decline in CD4 cells and decreases the
incidence of opportunistic infections.
8. Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
To convert their RNA into dsDNA, retroviruses
require virally encoded RNA-dependent DNA
polymerase (reverse transcriptase). Mammalian
RNA and DNA polymerases are sufficiently distinct
to permit a selective inhibition of the viral reverse
transcriptase.
Resistance emerges rapidly when NRTIs are used as
single agents via mutations in the pol gene; cross-
resistance occurs but is not complete.
9. Non-nucleoside reverse transcriptase inhibitors
(NNRTI)
NNRTIs bind to a site on reverse transcriptase
different from the binding site of NRTIs.
Nonnucleoside drugs do not require phosphorylation
to be active and do not compete with nucleoside
triphosphates. There is no cross-resistance with
NRTIs. Resistance from mutations in the pol gene
occurs very rapidly if these agents are used as
monotherapy
11. Protease inhibitors
The HIV protease inhibitors are designer drugs
based on molecular characterization of the active site
of the viral enzyme.
Resistance is mediated via multiple point mutations
in the pol gene; the extent of cross-resistance is
variable depending on the specific protease inhibitor.
Protease inhibitors (PIs) have important clinical use
in AIDS, most commonly in combinations with
reverse transcriptase inhibitors as components of
HAART.
12. Antinfluenza agents
Amantadine and rimantadine inhibit an early step in
replication of the influenza A (but not influenza B)
virus
They prevent “uncoating” by binding to a proton
channel. This protein functions as a proton ion
channel required at the onset of infection to permit
acidification of the virus core, which in turn activates
viral RNA transcriptase.
Adamantine-resistant influenza A virus mutants are
now common.
14. Interferons
Interferons are cytokines that act through host cell
surface receptors increasing the activity of Janus
kinases (JAKS). These enzymes phosphorylate signal
transducers and activators of transcription (STATS)
to increase the formation of antiviral proteins.
Interferon α is used for the treatment of hepatitis.
IFN-α also promotes formation of natural killer cells
that destroy infected liver cells.
