Page 289 - Review of Medical Microbiology and Immunology ( PDFDrive )

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PART III Basic Virology
278
virus-encoded thymidine kinase that phosphorylates the
drug. Acyclovir is not phosphorylated in uninfected cells, and
• Sofosbuvir inhibits RNA polymerase and is useful in the
cellular DNA synthesis is not inhibited. Selective toxicity is high,
treatment of chronic HCV infection.
and there are very few adverse effects.
• Ledipasvir inhibits NS5A protein of HCV thereby inhibiting
• Acyclovir is a chain-terminating drug because it lacks a
synthesis of the progeny RNA genomes of HCV.
hydroxyl group in the 3′ position. It does not have a ribose ring
(i.e., it is acyclo, meaning without a ring). The absence of this
hydroxyl group means the next nucleoside triphosphate can- Inhibitors of Other Viruses
not be added and the replicating DNA chain is terminated.
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• Ribavirin is a guanosine analogue that can inhibit nucleic acid
• Acyclovir inhibits viral replication but has no effect on the
synthesis of several viruses. It is useful in severe respiratory
latency of HSV-1, HSV-2, and VZV.
syncytial virus infections.
• Ganciclovir action is very similar to that of acyclovir, but it is effec-
tive against cytomegalovirus (CMV), whereas acyclovir is not.
• Raltegravir, elvitegravir, and dolutegravir inhibit the integrase
Inhibitors of Herpesviruses: Nonnucleoside Inhibitors
encoded by HIV, which blocks the integration of HIV DNA into
host cell DNA.
• Foscarnet inhibits the DNA polymerase of all herpesviruses
but is clinically useful against HSV and CMV. It is a pyrophos-
phate analogue that inhibits the cleavage of pyrophosphate
from the nucleoside triphosphate that has been added to the
• Indinavir and other similar drugs inhibit the virus-encoded
growing DNA chain. Protease Inhibitors
protease of HIV. Inhibition of the protease prevents cleavage
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mebooksfree.com mebooksfree.com mebooksfree.com • Boceprevir, simeprevir, telaprevir, and paritaprevir inhibit the mebooksfree.com
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of precursor polypeptides, which prevents formation of the
Inhibitors of Retroviruses: Nucleoside Inhibitors (NRTIs)
structural proteins of the virus. Synthesis of infectious virus is
inhibited, but the viral DNA integrated into the host cell DNA is
• Zidovudine inhibits the DNA polymerase (reverse transcrip-
unaffected.
tase) of HIV. It is a chain-terminating drug because it has an
azide group in place of the hydroxyl group in the 3′ position.
Unlike acyclovir, it does not require a viral-encoded kinase to be
protease of hepatitis C virus.
phosphorylated. Cellular kinases phosphorylate the drug, so it is
active in uninfected cells and significant adverse effects can occur.
Inhibitors of Viral Protein Synthesis
• Other drugs with the same mode of action include lamivudine,
• Interferons inhibit virus replication by degrading mRNA
didanosine, emtricitabine, stavudine, abacavir, and tenofovir.
and blocking protein synthesis. (See Chapter 33 for more
information.) Pegylated interferon-alpha is used in the treat-
Inhibitors of Retroviruses: Nonnucleoside Inhibitors
ment of chronic hepatitis B and acute hepatitis C.
(NNRTIs)
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mebooksfree.com mebooksfree.com mebooksfree.com • Fomivirsen is an antisense DNA that binds to the mRNA of CMV, mebooksfree.com
which prevents the mRNA from being translated into viral
• Nevirapine, delavirdine, efavirenz, etravirine, and rilpivirine
proteins.
inhibit the DNA polymerase (reverse transcriptase) of HIV
but are not nucleoside analogues.
Inhibitors of Release of Virus
Inhibitors of Hepatitis B Virus
• Zanamivir and oseltamivir inhibit the neuraminidase of
both influenza A and B viruses. This inhibits the release
• Adefovir, entecavir, lamivudine, and telbivudine inhibit the
of progeny virus, which reduces spread of virus to neigh-
DNA polymerase of hepatitis B virus (HBV). These drugs are
boring cells.
useful in the treatment of chronic HBV infection.
SELF-ASSESSMENT QUESTIONS (D) Ritonavir inhibits the virus-encoded protease that is required
to cleave viral precursor polypeptides into functional proteins.
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1. Regarding the mode of action of antiviral drugs, which one of the
(E) Zidovudine inhibits the virus-encoded RNA polymerase that is
following is the MOST accurate?
required to synthesize viral mRNA.
(A) Amantadine inhibits the virus-encoded DNA polymerase that
vir (Tamiflu)?
is required to synthesize viral progeny DNA.
(B) Lamivudine inhibits the cell-encoded RNA polymerase that is
(A) Inhibits reverse transcriptase
required to synthesize viral genome.
(B) Inhibits the RNA-dependent RNA polymerase in the virion
(C) Raltegravir inhibits the translation of viral mRNA into viral
(C) Inhibits the DNA-dependent RNA polymerase in the infected
proteins.
cell
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