Novel Inhibitor Design for Hemagglutinin against H1N1 Influenza Virus by Core Hopping Method

Li, Xiao-Bo; Wang, Shu-Qing; Xu, Wei-Ren; Wang, Run-Ling; Chou, Kuo-Chen

Influenza A virus that belongs to the Orthomyxoviridae family is a negative-strand segmented RNA virus, in which the surface membrane proteins are constituted by three important components: M2 proton channel, hemagglutinin (HA), and neuraminidase (NA). The M2 proton channel is responsible for proton conductance vitally important to viral replication. HA is responsible for binding to the surface of the infected cell as a trimer leading to the attachment and subsequent penetration by viruses into the target cell. NA is responsible for cleaving the terminal sialic acid moieties from the receptors to facilitate the elution of the progeny virions from the infected cell [4] . Therefore, any of the three components can be the target for drug design against influenza virus. Recently, stimulated by the successful determination of its high-resolution three-dimensional structure [5] , many discussions about the M2 channel have been made in this regard [5, 6, 7, 8, 9] . The two existing M2 drugs, amantadine (Symmetrel) [10] and rimantadine (Flumadine) [10] approved by FDA, are no longer effective because of their inefficacies to influenza virus.