Macrocycles to target influenza viral hemagglutinin as bifunctional potent broad-spectrum antiviral agent

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K15146
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: KOHARA Michinori 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 特任研究員 (10250218)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 特殊環状ペプチド / 治療 / インフルエンザ

Outline of Final Research Achievements

HA-targeted antibodies have the potential to neutralize HA-mediated virion-cell binding. To devise smaller molecules capable of binding to the influenza viral HA and have the potential as an antiviral agent, we used an emerging technology, RaPID system. After five rounds of selection, we found an appreciable increase in the cDNA recovery rate and sequencing of 69 molecular clones from the selected cDNAs revealed a total of 28 candidates for inhibitor HA (iHA). In order to investigate the influence of iHA-100 on the pathology of H5N1 infection, a comprehensive analysis of cytokines was performed. Inflammatory cytokines (IFN-ganma, IL-6) in the lung of iHA-100-treated monkeys were significantly reduced. These results suggest that H5N1-induced inflammation and pathogenesis was suppressed by administration of iHA-100. iHA-100 is a promising antiviral agent that exhibited the inhibitory effect of both virus replication and pathogenesis in vivo.

Free Research Field

感染免疫学