Page 282 - Review of Medical Microbiology and Immunology ( PDFDrive )

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immunodeficiency virus (HIV) mebooksfree.com
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CHAPTER 35 Antiviral Drugs
271
TABLE 35–3 Antiviral Drugs That Block Viral Nucleic Acid Synthesis
Mode of Action
Antiviral Drugs
1. Nucleoside inhibitors: acyclovir, ganciclovir, valacyclovir, valganciclovir,
Inhibition of DNA polymerase of herpesviruses
penciclovir, famciclovir, cidofovir, trifluridine
2. Nonnucleoside inhibitors: foscarnet
1. Nucleoside inhibitors: zidovudine, lamivudine, emtricitabine, didanosine,
Inhibition of reverse transcriptase of human
stavudine, abacavir, tenofovir
2. Nonnucleoside inhibitors: nevirapine, delavirdine, efavirenz, etravirine, rilpivirine
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Inhibition of reverse transcriptase of hepatitis B virus
Adefovir, entecavir, lamivudine, telbivudine
Sofosbuvir, dasabuvir
Inhibition of RNA polymerase of hepatitis C virus
Inhibition of NS5A protein of hepatitis C virus
Ledipasvir, ombitsavir
Ribavirin
Inhibition of nucleic acid synthesis by other viruses
Acyclovir is active primarily against HSV-1 and -2
and varicella-zoster virus (VZV). It is relatively non-
toxic, because it is activated preferentially within virus-
clovir monophosphate by the viral thymidine kinase,
infected cells. This is due to the virus-encoded
cellular kinases synthesize acyclovir triphosphate, which
inhibits viral DNA polymerase much more effectively
thymidine kinase, which phosphorylates acyclovir against CMV. Once the drug is phosphorylated to acy-
than it inhibits cellular DNA polymerase. Acyclovir
much more effectively than does the cellular thymidine
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causes chain termination because it lacks a hydroxyl
kinase. Because only HSV-1, HSV-2, and VZV encode a
kinase that efficiently phosphorylates acyclovir, the drug
group in the 3′ position.
inhibited by
palivizumab (RSV)

Virion

Receptor

Uncoating Nucleus
inhibited by
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amantadine
(influenza)
Progeny
genomes

mRNAs
Precursor
Assembly into
nucleocapsid
Nucleic acid
inhibited by
synthesis
oseltamivir and
inhibited by
Protein synthesis
(influenza)
inhibited by
1. Acyclovir - (HSV, VZV)
2. Ganciclovir - (CMV) 1. Interferon α and β Precursor zanamivir
(Interferon α used
3. Foscarnet - (HSV, CMV)
protein processing
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clinically against
4. Cidofovir - (CMV)
inhibited by
HBV and HCV)
5. Ribavirin - (RSV)
boceprevir and
2. Fomivirsen (CMV)
6. Adefovir, entecavir,
telaprevir (HCV)
telbivudine (HBV)
7. Sofosbuvir (HCV)
8. Ledipasvir (HCV)
FIGURE 35–1
Replicative cycle of a model virus showing the site of action of drugs used to treat various viral infections. CMV, cytomega-
lovirus; HBV, hepatitis B virus; HCV, hepatitis C virus; HSV, herpes simplex virus; RSV, respiratory syncytial virus; VZV, varicella-zoster virus.
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