A broad-spectrum virus- and host-targeting peptide against respiratory viruses including influenza virus and SARS-CoV-2.
Amino Acid Sequence
Animals
Antiviral Agents
/ chemistry
Cell Line
Coronavirus
/ drug effects
Endosomes
/ chemistry
Female
Humans
Hydrogen-Ion Concentration
Influenza A virus
/ drug effects
Mice
Mice, Inbred BALB C
Orthomyxoviridae Infections
/ drug therapy
Peptides
/ chemistry
Protein Binding
Protein Conformation
Rhinovirus
/ drug effects
Viral Load
/ drug effects
Virus Replication
/ drug effects
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
25 08 2020
25 08 2020
Historique:
received:
09
03
2020
accepted:
27
07
2020
entrez:
27
8
2020
pubmed:
28
8
2020
medline:
15
9
2020
Statut:
epublish
Résumé
The 2019 novel respiratory virus (SARS-CoV-2) causes COVID-19 with rapid global socioeconomic disruptions and disease burden to healthcare. The COVID-19 and previous emerging virus outbreaks highlight the urgent need for broad-spectrum antivirals. Here, we show that a defensin-like peptide P9R exhibited potent antiviral activity against pH-dependent viruses that require endosomal acidification for virus infection, including the enveloped pandemic A(H1N1)pdm09 virus, avian influenza A(H7N9) virus, coronaviruses (SARS-CoV-2, MERS-CoV and SARS-CoV), and the non-enveloped rhinovirus. P9R can significantly protect mice from lethal challenge by A(H1N1)pdm09 virus and shows low possibility to cause drug-resistant virus. Mechanistic studies indicate that the antiviral activity of P9R depends on the direct binding to viruses and the inhibition of virus-host endosomal acidification, which provides a proof of concept that virus-binding alkaline peptides can broadly inhibit pH-dependent viruses. These results suggest that the dual-functional virus- and host-targeting P9R can be a promising candidate for combating pH-dependent respiratory viruses.
Identifiants
pubmed: 32843628
doi: 10.1038/s41467-020-17986-9
pii: 10.1038/s41467-020-17986-9
pmc: PMC7447754
doi:
Substances chimiques
Antiviral Agents
0
Peptides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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