Drug design for hemagglutinin: Screening and molecular dynamics from traditional Chinese medicine database

Abstract

Since the outbreak of Swine flu, H1N1 virus had caused a global pandemic and resulted in more than 18,000 deaths over the world as dated on August 2010. Influenza virus surface glycoprotein, hemagglutinin, holds a critical role in mediating viral entry into host cell. Currently, there is no available hemagglutinin binding inhibitor, and already, influenza virus strains resistant to front-line antivirals have been discovered. Here, we report two rosmaricine derivatives might be potent leads which screening from the world largest traditional Chinese medicine database. The docking results shown the rosmaricine derivatives bind influenza hemagglutinin with high affinity based on binding energy. Both rosmaricine_5 and rosmaricine_16 have high binding energy and have hydrogen bonding with hemagglutinin sialic acid binding site residues, Glu83, Asp103 and Asn104. These interactions persist throughout the molecular dynamics simulation and keep the rosmaricine derivatives in the hemagglutinin sialic acid binding site. From the molecular dynamics results show that a potential hemagglutinin inhibitor should have a protonated amine for interacting with Asp103 and hydroxyl groups for interacting with Glu83 and Asn104. Overall, we suggest our two de novo compounds can become novel antivirals for treating influenza infection.