RESUMO
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.