Design, synthesis and activity of a new type of influenza virus N1 neuraminidase inhibitors.

In this study,the "150-cavity",next to the H5N1 influenza virus neuraminidase activity site,has been used as the target to design and synthesize a structural analogue of chlorogenic acid,N-caffeoyl-GABA,using the flexible docking simulation.The docking study showed that the N-caffeoyl-GABA could be inserted into the "150-cavity" and combined with the Arg156 side chain by hydrogen bond.The best binding free energy of H5N1 NA-N-caffeoyl-GABA complex was-7.70 kcal·mol-1,equivalent that of the NA-oseltamivir.At the same time,using the H5N1 pseudotyping virus-based NA inhibitors screening model,we determined the inhibitory effect of oseltamivir,chlorogenic acid and N-caffeoyl-GABA on the NA.Compared with chlorogenic acid,N-caffeoyl-GABA significantly enhanced the inhibitory effect on NA,but less than oseltamivir.This study showed that the "150-cavity" could possibly be used as a new neuraminidase inhibitors target,and provided a path for the development of new neuraminidase inhibitors.