Recent Strategies in the Search for New Anti-Influenza Therapies

Influenza is a highly contagious, acute upper respiratory tract disease caused by influenza virus, a member of the Orthomyxoviridae family. The viral particles have two surface antigens, haemagglutinin and sialidase (neuraminidase) that extensively decorate the surface of the virus and have been implicated in viral attachment and fusion, and the release of virion progeny, respectively. The receptor for haemagglutinin is the terminal sialic acid residue of host cell surface sialyloligosaccharides, while sialidase catalyses the hydrolysis of terminal sialic acid residues from sialyloligosaccharides. Extensive crystallographic studies of both these proteins have revealed that the residues that interact with the sialic acid are strictly conserved. Therefore, these proteins make attractive targets for the design of drugs to halt the progression of the virus. Recent successful efforts in the search for new cures for influenza have led to the development of three clinically-useful anti-influenza drugs. All three are potent, selective inhibitors of influenza virus A and B sialidase. Strategies for the development of haemagglutinin inhibitors have also been devised.