Development of highly active HIV fusion inhibitors

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K07158
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49060:Virology-related
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Murakami Tsutomu 国立感染症研究所, エイズ研究センター, 主任研究官 (50336385)
• Co-Investigator(Kenkyū-buntansha): 玉村 啓和 東京医科歯科大学, 生体材料工学研究所, 教授 (80217182)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: HIV / 膜融合 / 阻害剤 / 二量体化

Outline of Final Research Achievements

Membrane fusion is a valid target for inhibition of HIV-1 replication. A 34-mer fragment peptide (C34), which is contained in the HIV-1 envelope protein gp41, has significant anti-HIV activity. Previously, a dimeric derivative of C34 linked by a disulfide bridge at its C-terminus was found to have more potent anti-HIV activity than the C34 peptide monomer. To date, several peptidomimetic small inhibitors have been reported, but most have lower potency than peptide derivatives related to C34. In the present study we applied this dimerization concept to these peptidomimetic small inhibitors and designed several bivalent peptidomimetic HIV-1 fusion inhibitors. The importance of the length of linkers crosslinking two peptidomimetic compounds was demonstrated and several potent bivalent inhibitors containing tethered peptidomimetics were produced.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

HIV膜融合に関する新たな知見を提供し、さらにより強力なHIVHIV膜融合阻害剤開発に向けた新戦略を提供できた。