Influenza viral hemagglutinin-targeted macrocyclic peptides as an antiviral agent

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670224
• 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)
• Co-Investigator(Renkei-kenkyūsha): YASUI Fumihiko 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, 主席研究員 (40399473) ; MUNAKATA Tubasa 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, 主席研究員 (50420237) ; SAITO Makoto 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, 研究員 (20433021) ; MUNEKATA Keisuke 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, 研究員 (30569140) ; SUGA Hiroaki 東京大学, 大学院理学系研究科, 教授 (00361668)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: インフルエンザ / 特殊環状ペプチド / 感染阻害

Outline of Final Research Achievements

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 (Random non-standard Peptide Integrated Discovery) system. After five rounds selection of H5N1 HA-binding peptides, we found a total of 24 candidates for inhibitor HA (iHA).
iHA inhibited plaque formation against different clade H5N1 viruses, A/whooper swan/Mongolia/3/05 (H5N1/Mongolia; clade 2.2) and A/whooper swan/Hokkaido/1/08 (H5N1/Hokkaido; clade 2.3). Intriguingly, iHA was effective against pandemic (H1N1) 2009 viruses more than zanamivir. These results suggest that iHA is able to inhibit replication of a wide range of H1 and H5 influenza viruses via a mechanism of its interaction with HA. Polykaryon formation mediated by various clade H5 HAs were also inhibited by iHA in a dose-dependent manner.

Free Research Field

ウイルス学、感染免疫学