When viruses reproduce, they use much of the host’s own metabolic machinery. Therefore, few drugs are selective enough to prevent viral replication without injury to the host. Viruses are also not affected by antibacterial agents. Nevertheless, some drugs sufficiently discriminate between cellular and viral reactions to be effective and yet relatively nontoxic. For example, efficient management strategies are available for infections due to herpes simplex virus, varicella-zoster virus, cytomegalovirus, influenza A and B viruses, and chronic hepatitis B and C and HIV.

 A. Organization of viruses

The clinically important viruses can be conveniently divided into seven groups based on the nature of their genome, symmetry of organization, and the presence or absence of a lipid envelope (Figure .1). The therapeutic applications of selected antiviral agents are shown in Figure 2.

Fig1. Medically important viruses organized into similar groups based on the nature of the genome and the presence or absence of a lipid envelope.

Fig2. Summary of therapeutic applications of selected antiviral agents.

B. Treatment of herpesvirus infections

Most antiviral agents used in treating herpesvirus infections are nucleoside analogues that require conversion to mono-, di-, and triphosphate forms by cellular kinases, viral kinases, or both to selectively inhibit viral DNA synthesis. This class of antiviral agents includes acyclovir, cidofovir, famciclovir, ganciclovir, penciclovir, valacyclovir, valganciclovir, fomivirsen and vidarabine. A second class of antiviral drugs with action against herpesviruses is represented by the pyrophosphate analogue, foscarnet. Most antiviral agents, including nucleoside analogues and foscarnet, exert their actions during the acute phase of viral infections and are without effect in the latent phase.

C. Treatment of acquired immunodeficiency syndrome

 Antiretroviral drugs are divided into five main classes based on their mode of inhibition of viral replication. The first class represents nucleoside analogs that inhibit the viral RNA–dependent DNA polymerase (reverse transcriptase) of HIV. A second class of reverse transcriptase inhibitors includes nonnucleoside analogs. The third class includes protease inhibitors. The fourth class is a fusion inhibitor that prevents HIV from entering the host cell. The fifth class, integrase inhibitors, blocks the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell. Therapy with these antiretroviral agents, usually in combinations (a “cocktail” of drugs referred to as highly active antiretroviral therapy, or HAART), is beneficial to prolong survival, to reduce the incidence and severity of opportunistic infections in patients with advanced HIV disease (by allowing at least partial recovery of CD4 lymphocyte populations), and to delay disease progression in asymptomatic HIV-infected patients.

 D. Treatment of viral hepatitis

 Prolonged (months) treatment with interferon-α has succeeded in reducing or eliminating indicators of hepatitis B virus replication in about one third of patients. However, recurrence of indications of the infection may occur after therapy cessation. Lamivudine, an oral nucleoside analogue, is an effective treatment in patients with previously untreated chronic hepatitis B. However, only a minority of patients is cured or remains in remission after lamivudine therapy is withdrawn. Maintenance therapy may be indicated, but long-term use of lamivudine is limited by the appearance of viral polymerase gene mutants, which leads to reemergence of disease. The therapy of choice for hepatitis C is interferon-α in combination with ribavirin. The overall rate of response to this drug combination is three times greater than that seen with interferon-α monotherapy. However, anemia is a common adverse effect induced by ribavirin.

E. Treatment of influenza

Zanamivir and oseltamivir are effective against influenza A and B. They inhibit viral neuraminidase, thereby preventing the release of virus from infected cells.

مواضيع ذات صلة

Entry and Integrase Inhibitors

Protease Inhibitors

Non-nucleoside Reverse Transcriptase Inhibitors

Nucleoside and Nucleotide Reverse Transcriptase Inhibitors

Introduction to Antiretroviral Drugs

Neuramidase Inhibitors

Anti-Cytomegalovirus Agents

Anti-Herpes Simplex Virus and Varicella-Zoster Virus Agents

Introduction to Antiviral Drugs