Application of molecular dynamics simulation to construct of virtual assay system of antiviral drug resistance

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15420
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Hokkaido University
• Principal Investigator: Sakamoto Naoya 北海道大学, 医学研究院, 教授 (10334418)
• Co-Investigator(Kenkyū-buntansha): 須田 剛生 北海道大学, 大学病院, 特任助教 (20447460) ; 森川 賢一 北海道大学, 大学病院, 助教 (60384377)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: ウイルス肝炎

Outline of Final Research Achievements

We conducted molecular dynamics simulation assay to construct docking models of direct acting antivirals and the target viral protein and studied effects of resistance-associated mutations of the viral protein on the drug-protein binding affinity and the drug resistance. We further conducted in-vitro HCV replicon cell culture system and confirmed significant association of the calculated binding affinity and the phenotypic drug resistance. We confirmed that NS5A-P32del resistance mutation acquires strong resistance to all clinically available NS5A inhibitors in vitro.

Free Research Field

消化器内科学