Approaches and strategies for the treatment of influenza virus infections

Influenza A and B viruses belong to the Orthomyxoviridae family of viruses. These viruses are responsible for severe morbidity and significant excess mortality each year. Infection with influenza viruses usually leads to resp iratory involvement and can result in pneumonia and secondary bacterial inf ections. Vaccine approaches to the prophy-laxis of influenza virus infectio ns have been problematic owing to the ability of these viruses to undergo a ntigenic shift by exchanging genomic segments or by undergoing antigenic dr ift, consisting of point mutations in the haemagglutinin (HA) and neuramini dase (NA) genes as a result of an error-prone viral polymerase. Historicall y, antiviral approaches for the therapy of both influenza A and B viruses h ave been largely unsuccessful until the elucidation of the X-ray crystallog raphic structure of the viral NA, which has permitted structure-based drug design of inhibitors of this enzyme. In addition, recent advances in the el ucidation of the structure and complex function of influenza HA have result ed in the discovery of a number of diverse compounds that target this viral protein. This review article will focus largely on newer antiviral agents including those that inhibit the influenza virus NA and HA. Other novel app roaches that have entered clinical trials or been considered for their clin ical utility will be mentioned.