Potent peptidic fusion inhibitors of influenza virus
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.
- Publication Date:
- Research Org.:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- National Institutes of Health (NIH)
- OSTI Identifier:
- 1408128
- Resource Type:
- Journal Article
- Resource Relation:
- Journal Name: Science; Journal Volume: 358; Journal Issue: 6362
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 60 APPLIED LIFE SCIENCES
Citation Formats
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., and Wilson, Ian A. Potent peptidic fusion inhibitors of influenza virus. United States: N. p., 2017.
Web. doi:10.1126/science.aan0516.
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. Potent peptidic fusion inhibitors of influenza virus. United States. doi:10.1126/science.aan0516.
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., and Wilson, Ian A. Thu .
"Potent peptidic fusion inhibitors of influenza virus". United States.
doi:10.1126/science.aan0516.
@article{osti_1408128,
title = {Potent peptidic fusion inhibitors of influenza virus},
author = {Kadam, Rameshwar U. and Juraszek, Jarek and Brandenburg, Boerries and Buyck, Christophe and Schepens, Wim B. G. and Kesteleyn, Bart and Stoops, Bart and Vreeken, Rob J. and Vermond, Jan and Goutier, Wouter and Tang, Chan and Vogels, Ronald and Friesen, Robert H. E. and Goudsmit, Jaap and van Dongen, Maria J. P. and Wilson, Ian A.},
abstractNote = {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.},
doi = {10.1126/science.aan0516},
journal = {Science},
number = 6362,
volume = 358,
place = {United States},
year = {Thu Sep 28 00:00:00 EDT 2017},
month = {Thu Sep 28 00:00:00 EDT 2017}
}
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