Investigation for novel antiviral lead compounds focusing on the host adaptation mechanism of influenza virus

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15171
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49060:Virology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Arai Yasuha 京都府立医科大学, 医学(系)研究科(研究院), 研究員 (80793182)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: インフルエンザウイルス / 宿主因子 / ヒト適応性 / ウイルス複製

Outline of Final Research Achievements

We have identified novel adaptive mutations in humans by comprehensively searching for adaptive mutations acquired by avian influenza virus in infected patients. The purpose of this study was to identify host factors essential for viral replication using the mutant viruses as human adaptation model viruses.
We established an immunoprecipitation method that efficiently coprecipitates host factors that bind to polymerase complex, and selected multiple host factors that specifically bind to mutants by LC-MS / MS. We evaluated the effect of this factor on viral replication, but the factors that affect viral replication have not been identified. We are trying to select candidate factors more widely and create multiple knockdown cells.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

ウイルス複製に重要な宿主因子を同定し、さらに宿主因子・ウイルス蛋白質の結合を阻害するリード化合物探索へ研究を展開する。現存の抗インフルエンザ薬は、特定のウイルス蛋白質の働きを抑えるが、ウイルス遺伝子の変異によって薬剤耐性ウイルスが出現する問題点がある。今後同定されるリード化合物は、ウイルス蛋白質に作用せずにその複製を阻害するため、既存の抗ウイルス薬の弱点を克服できる可能性がある。