Computational Studies of Influenza A Virus at Three Important Targets: Hemagglutinin, Neuraminidase and M2 Protein

Thanyada      Rungrotmongkol; Pathumwadee      Yotmanee; Nadtanet      Nunthaboot; Supot      Hannongbua

Abstract

While the seasonal influenza viruses spreading around the world cause the annual epidemics, the recent outbreaks of influenza A virus subtype H5N1 and pandemic H1N1 have raised global human health concerns. In this review, the applicabilities of computational techniques focused on three important targets in the viral life cycle: hemagglutinin, neuraminidase and M2 proton channel are summarized. Protein mechanism of action, substrate binding specificity and drug resistance, ligand-target interactions of substrate/ inhibitor binding to these three proteins either wild-type or mutant strains are discussed and compared. Advances on the novel antiinfluenza agents designed specifically to combat the avian H5N1 and pandemic H1N1 viruses are introduced. A better understanding of molecular inhibition and source of drug resistance as well as a set of newly designed compounds is greatly useful as a rotational guide for synthetic and medicinal chemists to develop a new generation of anti-influenza drugs.

Keywords: Avian influenza H5N1 virus, pandemic influenza H1N1 virus, hemagglutinin, neuraminidase, M2 channel, theoretical calculations, computer-aided drug design, influenza, pandemic influenza, avian flu, Orthomyxoviridae, glycoproteins, galactose, proteolysis, homotrimer, pathogenicity, polybasic, chymotrypsin, nucleophile, imidazolium