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Chapter 35: Antiviral Drugs

PRINCIPLES OF ANTIVIRAL THERAPY

Compared with the number of drugs available to treat bacterial infections, the number of antiviral drugs is very small. The major reason for this difference is the difficulty in obtaining selective toxicity against viruses; their replication is intimately involved with the normal synthetic processes of the cell. Despite the difficulty, several virus-specific replication steps have been identified that are the site of action of effective antiviral drugs (Table 35–1). Table 35–2 describes the mode of action of antiviral drugs that block early events in viral replication, and Table 35–3 describes the mode of action of antiviral drugs that block viral nucleic acid synthesis. Figure 35–1 shows the replication of a model virus and the site of action of drugs used to treat various viral infections. Figure 35–2 shows the replication of human immunodeficiency virus (HIV) and the site of action of drugs used to treat HIV infection.

Table 35–1Stage of Viral Replication Inhibited by Antiviral Drugs
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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
Nucleic acid synthesis by herpesviruses Acyclovir, ganciclovir, valacyclovir, valganciclovir, penciclovir, famciclovir, cidofovir, trifluridine, foscarnet
Nucleic acid synthesis by human immunodeficiency virus (HIV) Zidovudine, lamivudine, emtricitabine, didanosine, stavudine, abacavir, tenofovir, nevirapine, delavirdine, efavirenz, etravirine, rilpivirine
Nucleic acid synthesis by hepatitis B virus (HBV) Adefovir, entecavir, lamivudine, telbivudine, tenofovir
Nucleic acid synthesis by hepatitis C virus (HCV)

RNA polymerase inhibitors: sofosbuvir, dasabuvir

NS5A inhibitors: ledipasvir, ombitasvir
Nucleic acid synthesis by other viruses Ribavirin
Cap-snatching to produce viral m-RNA by influenza virus Baloxavir
Integrase that integrates HIV DNA into cellular DNA Raltegravir, elvitegravir, dolutegravir
Cleavage of precursor DNA by cytomegalovirus Letermovir
Cleavage of precursor polypeptides

Protease inhibitors of HIV: saquinavir, indinavir, ritonavir, nelfinavir, amprenavir, atazanavir, darunavir, lopinavir, tipranavir

Protease inhibitors of hepatitis C virus: boceprevir, simeprevir, telaprevir, paritaprevir
Protein synthesis directed by viral mRNA Interferon, fomivirsen
Release of influenza virus from infected cell Oseltamivir, zanamivir
Table 35–2Antiviral Drugs that Block Early Events
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Table 35–2 Antiviral Drugs that Block Early Events
Antiviral Drug Mode of Action Virus Inhibited
Amantadine, rimantadine Inhibits uncoating by blocking M2 matrix protein Influenza virus
Enfuvirtide Inhibits fusion by binding to gp41 of human immunodeficiency virus (HIV) HIV
Maraviroc Inhibits attachment to cell surface receptor CCR-5 HIV
Ibalizumab Monoclonal antibody against CD4 protein that blocks binding of HIV to CCR-5 and CXCR-4 coreceptors HIV
Palivizumab Monoclonal antibody that blocks binding of viral fusion protein to receptor on respiratory mucosal cell Respiratory syncytial virus
Table 35–3Antiviral Drugs that Block Viral Nucleic Acid Synthesis
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Table 35–3 Antiviral Drugs that Block Viral Nucleic Acid Synthesis
Mode of Action Antiviral Drugs
Inhibition of ...

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