Exploitation of macrocyclic peptides that show inhibitory effect on influenza virus infection

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860096
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: 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, 主任研究員 (20433021)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 特殊環状ペプチド / インフルエンザウイルス / ヘマグルチニン / 高病原性H5N1 / H1N1 / H2N2 / 感染阻害活性

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 RaPID (Random non-standard Peptide Integrated Discovery) system. After five rounds of selection, we found 4 candidates of macrocyclic peptides. These candidates inhibit H5N1 viruses replication. Intriguingly, one of the candidates was also effective against H1N1 and H2N2 viruses more than zanamivir. These results suggest that the macrocyclic peptide is able to inhibit replication of a wide range of Group 1 influenza viruses via a mechanism of its interaction with HA. Furthermore, we evaluated the in vivo efficacy of the macrocyclic peptide against highly pathogenic H5N1 infection in a murine lethal infection model. The macrocyclic peptide showed higher therapeutic potential compared with zanamivir. Taken together, we could identify a new class of HA-targeted broad-spectrum antiviral candidates for influenza treatment.

Free Research Field

ウイルス学