Page 281 - Review of Medical Microbiology and Immunology ( PDFDrive )

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PART III Basic Virology
270
TABLE 35–1 Stage of Viral Replication Inhibited by Antiviral Drugs
Stage of Viral Replication Inhibited
Effective Antiviral Drugs
Early events (entry or uncoating of the virus)
Amantadine, rimantadine, enfuvirtide, maraviroc, palivizumab
Acyclovir, ganciclovir, valacyclovir, valganciclovir, penciclovir, famciclovir,
Nucleic acid synthesis by herpesviruses
cidofovir, trifluridine, foscarnet
Nucleic acid synthesis by human immunodeficiency
tenofovir, nevirapine, delavirdine, efavirenz, etravirine, rilpivirine
virus (HIV)
Nucleic acid synthesis by hepatitis B virus (HBV) Zidovudine, lamivudine, emtricitabine, didanosine, stavudine, abacavir,
Adefovir, entecavir, lamivudine, telbivudine, tenofovir
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RNA polymerase inhibitors: sofosbuvir, dasabuvir
Nucleic acid synthesis by hepatitis C virus (HCV)
NS5A inhibitors: ledipasvir, ombitsavir
Ribavirin
Nucleic acid synthesis by other viruses
Raltegravir, elvitegravir, dolutegravir
Integrase that integrates HIV DNA into cellular DNA
Protease inhibitors of HIV: saquinavir, indinavir, ritonavir, nelfinavir, amprenavir,
Cleavage of precursor polypeptides
atazanavir, darunavir, lopinavir, tipranavir
Protease inhibitors of hepatitis C virus: boceprevir, simeprevir, telaprevir,
paritaprevir
Interferon, fomivirsen
Protein synthesis directed by viral mRNA
Oseltamivir, zanamivir
Release of influenza virus from infected cell
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Despite its efficacy in preventing influenza, it is not
widely used in the United States because the vaccine is pre-
tract mucosal cells. It is used to prevent bronchiolitis and
ferred for the high-risk population. Furthermore, most
pneumonia in premature or immunocompromised infants.
isolates have become resistant to amantadine. The main side
effects of amantadine are central nervous system altera-
INHIBITION OF VIRAL NUCLEIC
tions such as dizziness, ataxia, and insomnia. Rimantadine
(Flumadine) is a derivative of amantadine and has the same
ACID SYNTHESIS
mode of action but fewer side effects.
Inhibitors of Herpesviruses
Enfuvirtide (Fuzeon) is a synthetic peptide that binds
to gp41 on the surface of HIV, thereby blocking the entry of
Nucleoside Inhibitors
the virus into the cell. It is the first of a new class of anti-
These drugs are analogues of nucleosides that inhibit the
HIV drugs known as “fusion inhibitors” (i.e., they prevent
DNA polymerase of one or more members of the herpesvi-
the fusion of the viral envelope with the cell membrane).
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Maraviroc (Selzentry) blocks the binding of HIV to
merase herpes simplex virus types 1 and 2 (HSV-1 and -2)
CCR-5—an important coreceptor for those strains of HIV
and varicella-zoster virus but not cytomegalovirus (CMV).
that use CCR-5 for entry into the cell. The drug binds to
1. Acyclovir—Acyclovir (acycloguanosine, Zovirax) is a
CCR-5 and blocks the interaction of gp120, an HIV enve-
lope protein, to CCR-5 on the cell surface.
guanosine analogue that has a three-carbon fragment in
Palivizumab (Synagis) is a monoclonal antibody
place of the normal sugar, ribose, which has five carbons
(see Figure 35–3). The term acyclo refers to the fact that
directed against the fusion protein of respiratory syncytial
the three-carbon fragment does not have a sugar ring
virus (RSV). Palivizumab neutralizes RSV by binding to the
fusion protein on the surface of RSV, thereby preventing the
structure (a = without, cyclo = ring).
TABLE 35–2 Antiviral Drugs That Block Early Events
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Antiviral Drug
Virus Inhibited
Amantadine, rimantadine
Influenza virus
Inhibits uncoating by blocking M2 matrix protein
HIV
Enfuvirtide
Inhibits fusion by binding to gp41 of human immunodeficiency virus (HIV)
HIV
Inhibits attachment to cell surface receptor CCR-5
Maraviroc
Respiratory syncytial virus
Palivizumab
Monoclonal antibody that blocks binding of viral fusion protein to receptor
on respiratory mucosal cell
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