Jatrorrhizine hydrochloride potentiates the neuraminidase inhibitory effect of oseltamivir towards H7N9 influenza
A Chinese natural product,jatrorrhizine hydrochloride(JH),exhibited a potent inhibitory effect toward neuraminidase of the H7N9(N9)avian influenza virus.The interaction between JH and N9 was modeled using the molecular docking software AutoDock Similar to the control drug oseltamivir,JH bound into the active site of N9,but its position did not overlap with the position of oseltamivir.In addition,JH and oseltamivir were simultaneously docked into the active site of N9s(N9WT and N9R294K).By analyzing the docking result of the binding position,hydrogen bond interaction,and pi-pi interaction,N9 inhibition was likely enhanced by the combination of JH and oseltamivir.Molecular dynamics simulations using GROMACS were used to obtain trajectories of N9s and two compound complexes(JH was chosen from the docking result,whereas oseltamivir was directly extracted from the crystal structure)and to validate key interactions.The coordination between JH and oseltamivir to inhibit neuraminidase activity was further confirmed by the enzymatic assays of N9s.This study introduces novel treatment strategies to target N9 for a potential anti-H7N9 influenza drug.
Ye Wang Miao Yu Xiaonan Wang Xin Zhang Xizhu Wang Xuexun Fang
School of Life Science,Jilin University,2699 Qianjin Street,Changchun 130012,China Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education,Jilin University,26 The Second Affiliated Hospital of Mudanjiang Medical College,3 Xiaoyun Street,Mudanjiang 157009,Chin Department of Pharmacy,The First Affiliated Hospital of Jilin University,71 Xinmin Street,Changchun
国内会议
大连
英文
529-535
2016-09-24（万方平台首次上网日期，不代表论文的发表时间）