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Science. 2017 Oct 27;358(6362):496-502. doi: 10.1126/science.aan0516. Epub 2017 Sep 28.

Potent peptidic fusion inhibitors of influenza virus.

Author information

1
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
2
Janssen Prevention Center, Leiden, Netherlands.
3
Discovery Sciences, Janssen Research & Development, Beerse, Belgium.
4
Janssen Infectious Diseases and Vaccines, Beerse, Belgium.
5
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
6
Janssen Prevention Center, Leiden, Netherlands. mvandon@its.jnj.com wilson@scripps.edu.
7
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA. mvandon@its.jnj.com wilson@scripps.edu.
8
The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA.

Abstract

Influenza therapeutics with new targets and mechanisms of action are urgently needed to combat potential pandemics, emerging viruses, and constantly mutating strains in circulation. We report here on the design and structural characterization of potent peptidic inhibitors of influenza hemagglutinin. The peptide design was based on complementarity-determining region loops of human broadly neutralizing antibodies against the hemagglutinin (FI6v3 and CR9114). The optimized peptides exhibit nanomolar affinity and neutralization against influenza A group 1 viruses, including the 2009 H1N1 pandemic and avian H5N1 strains. The peptide inhibitors bind to the highly conserved stem epitope and block the low pH-induced conformational rearrangements associated with membrane fusion. These peptidic compounds and their advantageous biological properties should accelerate the development of new small molecule- and peptide-based therapeutics against influenza virus.

Comment in

PMID:
28971971
PMCID:
PMC5659926
DOI:
10.1126/science.aan0516
[Indexed for MEDLINE]
Free PMC Article

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