Antiviral agents active against influenza A viruses

Key Points

• Several drugs are available that could be used, either alone or in combination, for the treatment (prophylaxis or therapy) of an influenza pandemic. These include adamantan(amin)e derivatives (amantadine), neuraminidase inhibitors (zanamivir and oseltamivir), ribavirin and interferon.

• Amantadine was the first synthetic compound shown to inhibit influenza-virus replication. It blocks the migration of H ⁺ ions into the interior of the virus particles within endosomes, a process that is needed for uncoating to occur.

• Neuraminidase inhibitors such as oseltamivir and zanamivir interfere with the release of progeny influenza virions from the surface of infected host cells. In doing so, the neuraminidase inhibitors prevent virus infection of new host cells and thereby halt the spread of infection in the respiratory tract.

• Ribavirin targets a cellular enzyme — inosine 5′-monophosphate dehydrogenase, which has a key role in the biosynthesis of GTP and viral RNA synthesis — and is active against both human and avian influenza viruses.

• In addition to the available drugs, attempts to further design and develop new antivirals should be intensified, whether based on known molecular targets, such as the neuraminidase or viral uncoating process, or on as-yet relatively unexplored targets such as viral RNA polymerase.

Abstract

There are currently serious concerns about the control measures that should be taken if a pandemic of influenza A were to strike. De Clercq discusses the therapeutic potential of agents that have been shown to be active against influenza A viruses, and describes emerging strategies for targeting these viruses.

Abstract

The recent outbreaks of avian influenza A (H5N1) virus, its expanding geographic distribution and its ability to transfer to humans and cause severe infection have raised serious concerns about the measures available to control an avian or human pandemic of influenza A. In anticipation of such a pandemic, several preventive and therapeutic strategies have been proposed, including the stockpiling of antiviral drugs, in particular the neuraminidase inhibitors oseltamivir (Tamiflu; Roche) and zanamivir (Relenza; GlaxoSmithKline). This article reviews agents that have been shown to have activity against influenza A viruses and discusses their therapeutic potential, and also describes emerging strategies for targeting these viruses.