Computer Aid Drug Design of Novel Inhibitors of Influenza Based on the Crystal Neuraminidase Structure

• 1、1.School of Pharmacy, Tianjin Medical University, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, Tianjin 300070, China
• 2、 2. Tianjin Key Lab of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China

Abstract：Objectives：To observer high activity agents of NA against H5N1 Swine Influenza Virus, one novel classe of inhibitors have been discovered, that would indicate the further research. Methods: The small molecule database of lead-now were high-throughput screened by Glide of Schrodinger Suite 2009, and the candidates were optimized by Core Hopping of Schrodinger Suite 2009; the 10ns MD simulation of NA protein with and without candidates were performed by software Desmond4.2.Results: ZINC13219479, a cyclopentane ring compound, was screened from the database, and 8 novel compounds were optimized by generating its side-chain towards 150-cavity. To guide the further research, the database of small molecules was established. Final results of MD simulations were exposed the stable combination of complex, and confirmed the binging site. The inhibitors, small molecules designed on silicon according to formed H-bond between the compounds and 150-cavity of enzyme NA, performed the strong interaction and negative effects to the receptor. Conclusions: One group of novel inhibitors, had been screened and optimized accord with the combinational mode between and NA, were obtained by Schrodinger Suite 2009, as well confirmed the combinational activities by molecular dynamics simulation by Desmond 2.4.

Keywords： neuraminidase influenza virus CADD Oseltamivir 150-cavity