Potent peptidic fusion inhibitors of influenza virus

Kadam, Rameshwar U.; Juraszek, Jarek; Brandenburg, Boerries; Buyck, Christophe; Schepens, Wim B.  G.; Kesteleyn, Bart; Stoops, Bart; Vreeken, Rob J.; Vermond, Jan; Goutier, Wouter; Tang, Chan; Vogels, Ronald; Friesen, Robert H.  E.; Goudsmit, Jaap; van Dongen, Maria J.  P.; Wilson, Ian A.

doi:10.1126/science.aan0516

Title: Potent peptidic fusion inhibitors of influenza virus

Journal Article · Thu Sep 28 00:00:00 EDT 2017 · Science

DOI:https://doi.org/10.1126/science.aan0516· OSTI ID:1408128

;

; Vogels, Ronald; Friesen, Robert H. E.; Goudsmit, Jaap;

;

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.

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Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institutes of Health (NIH)

OSTI ID:: 1408128

Journal Information:: Science, Vol. 358, Issue 6362; ISSN 0036-8075

Publisher:: AAAS

Country of Publication:: United States

Language:: ENGLISH

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