Elucidation of a novel virus replication mechanism using compounds that inhibit bovine leukemia virus infection

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K06450
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42030:Animal life science-related
• Research Institution: Dokkyo Medical University (2020-2023); Institute of Physical and Chemical Research (2019)
• Principal Investigator: SATO Hirotaka 獨協医科大学, 医学部, 助教 (00708539)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: BLV / 感染症 / 抗ウイルス薬 / 阻害剤 / 作用機序解析 / 膜融合阻害 / 低分子化合物

Outline of Final Research Achievements

From previous research, five candidate compounds were found to have inhibitory effects against bovine leukemia virus infection. For each of these, screening was conducted on related compounds (a total of 275 compounds), and finally three compound structures with viral replication inhibitory activity were found. Additionally, lead compounds with higher activity and lower cytotoxicity (compounds A, B, and C) representing each of these structures were successfully obtained. Among these, compound C was suggested to act at a step after reverse transcription of the viral genome but before transcription of mRNA. Furthermore, it was revealed that compound B inhibits the cell fusion process in which the viral envelope and cell membrane fuse.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

本研究では牛伝染性リンパ腫ウイルス(BLV)の感染を抑制する作用を持つ薬剤について、より活性が高く、毒性の低い薬剤候補を見いだすことができた。これにより作用機序および作用標的の解析が可能になった。また、1化合物についてはその作用機序が細胞膜融合の阻害によるものである事までを明らかにする事ができた。このことは抗BLV薬剤候補として開発していくために重要な発見であった。この薬剤の標的分子を明らかにすることでBLVやその他ウイルスの感染における膜融合機構について新たな知見が得られるものと期待される。