ABSTRACT
The key details relating to mechanism of action, clinical indications, resistance mechanisms and toxicity of all currently licensed antiviral agents (except those for the treatment of HIV infection, see Topic E5) are shown in Table 1 .
(1) Anti-HSV and VZV agents Aciclovir
Basis of selectivity: Requires triphosphorylation, the first stage of which is performed by a viral enzyme, thymidine kinase. The drug therefore becomes activated and concentrated only in virally infected cells. Aciclovir triphosphate has a much higher affinity for viral DNA polymerase than for cellular DNA polymerase.
Analogues: Valaciclovir is a valine ester of aciclovir which is better absorbed orally. Penciclovir is a structural analogue with the same mechanism of action. It is also administered orally in the form of an ester, famciclovir.
Spectrum of activity: Aciclovir and analogues only work against those viruses able to phosphorylate them, i.e. herpes simplex and varicella-zoster viruses.
(2) Anti-CMV agents Ganciclovir
Basis of selectivity: Similar to aciclovir. Requires triphosphorylation, the first step being mediated by a viral enzyme, the UL97 protein. However, normal cells can also phosphorylate ganciclovir, resulting in greater toxicity than with aciclovir.
Analogues: Valganciclovir, the valine ester, is much better absorbed orally.
Spectrum of activity: CMV, as well as HSV and VZV.
Cidofovir
Basis of selectivity: Cidofovir triphosphate has much greater affinity for viral DNA polymerases than cellular DNA polymerase.
Spectrum of activity: Much broader than aciclovir, with potential activity against all DNA viruses.
Foscarnet
Basis of selectivity: Much greater affinity for viral DNA polymerases than cellular DNA polymerase.
Spectrum of activity: All herpesviruses.
(3) Antirespiratory vims agents Ribavirin
Spectrum of activity: In vitro has a broad spectrum, but in clinical practise is used only for treatment of severe RSV infection (inhalation of aerosolized drug), Lassa fever, and chronic hepatitis C virus infection.
221 Amantadine
Spectrum of activity: Extremely narrow – influenza A viruses only.
Zanamavir and oseltamivir
Spectrum of activity: All influenza viruses.
(4) Antihepatitis virus agents Interferon
Interferons (IFN) are naturally occurring protein molecules produced by cells in response to antigenic or viral stimuli. There are several IFN (α, β, and γ), produced by different cells.
Spectrum of activity: Theoretically broad, but in practise limited. IFN-α is useful in the treatment of some patients with chronic hepatitis B virus infection, where the mode of action is through immunomodulation. In chronic hepatitis C virus infection, IFN conjugated to polyethylene glycol (PEG-IFN) plus ribavirin combination therapy results in sustained virus clearance in ~ 50% of patients.
Lamivudine
Spectrum of activity: Chronic HBV infection (also HIV, see Topic E5).
Adefovir
Spectrum of activity: Chronic HBV infection.
