Analysis of novel resistance-associated substitutions of direct-acting antivirals for hepattis C virus

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15821
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kagoshima University
• Principal Investigator: Mawatari Seiichi 鹿児島大学, 医歯学域医学系, 助教 (50735339)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 薬剤耐性変異 / C型肝炎ウイルス / 直接作用型抗ウイルス薬

Outline of Final Research Achievements

Direct-acting antivirals (DAAs) for hepatitis C virus (HCV) have shown high rates of sustained virologic response (SVR). However, resistance-associated substitutions (RASs) are a cause of treatment failure. In the present study, we demonstrated that the patients who failed to Glecaprevir (GLE) and Pibrentasvir (PIB) therapy had co-existence of Q24K, L28M, R30E, and A92K RASs in the NS5A region. In addition, these RAS had severe resistance to NS5A inhibitors, including PIB in the analysis of replicons introduced co-existence of these RASs.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

実臨床において，Glecaprevir (GLE)+Pibrentasvir (PIB)の治療不成功に関連する薬剤耐性変異は報告されていたが，in vitro実験系で証明した報告はない．特に今回NS5A共変異に対するPIBなどのNS5A阻害剤に対する薬剤耐性について初めて明らかにした．本研究は，特にC型肝炎に対する直接作用型抗ウイルス薬の治療不成功者への治療戦略に役立つことが期待された．