Pharmacophore Virtual Screening for Finding Influenza A M2 Channel Inhibitors
The M2 proton channel of influenza A virus is essential to viral replication. The long-sought three-dimensional structure of the M2 proton channel of influenza A virus was successfully determined recently through high-resolution NMR. An alternative strategy for the rational design of new M2 channel inhibitors is enabled by the availability of 3D structure information on rimantadine in complex with the channel protein. A ligand-based computational approach has been used to generate specific 3D pharmacophore hypotheses based on rimantadine interactions with the proton channel, by implementing Catalyst software. The hypotheses represent prominent interactions and the chemical nature and the information about their binding to the active site. Secondly, the Traditional Chinese Medicine Database (TCMD), National Cancer Institute (NCI) database and also in-house database were chosen to do the first virtual screening by utilizing filtering technique and a series of new potent inhibitors were identified. The 122 compounds chosen through virtual screening were mapped with higher fit value (more than 0.9). The hits were then evaluated by their structures’ novelty, synthetic feasibility, toxicity, pharmokinetics as well as “Rule of Five. Due to the physical and chemical properties and structure novelty, 18 compounds finally were picked up and were docked on the active site of the M2 proton channel to predict their binding mode and binding affinities by using DOCK software. Based on the docking result, we integrated the different parameters to get the best binding mode.
M2 proton channel influenza A virus antivirus catalyst docking drug design
Liang Zhidan Shi Liuqing Wei Jing
Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science
国际会议
International Symposium on Crystal Engineering and Drug Delivery System 2009(2009晶体工程与药物传送系统国际会议)
天津
英文
395-396
2009-09-05（万方平台首次上网日期，不代表论文的发表时间）