Inhibition of Coronavirus Entry
Amino Acid Sequence
Animals
Antiviral Agents
/ chemistry
Betacoronavirus
/ chemistry
COVID-19
Chlorocebus aethiops
Coronavirus Infections
/ prevention & control
HEK293 Cells
Humans
Lipopeptides
/ chemistry
Membrane Fusion
/ drug effects
Middle East Respiratory Syndrome Coronavirus
/ chemistry
Pandemics
/ prevention & control
Pneumonia, Viral
/ prevention & control
Protein Domains
Respiratory Mucosa
/ drug effects
Severe acute respiratory syndrome-related coronavirus
/ chemistry
SARS-CoV-2
Spike Glycoprotein, Coronavirus
/ chemistry
Vero Cells
Virus Internalization
/ drug effects
SARS-CoV-2
fusion inhibitor
lipopeptide
spike protein
Journal
mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231
Informations de publication
Date de publication:
20 10 2020
20 10 2020
Historique:
entrez:
21
10
2020
pubmed:
22
10
2020
medline:
5
11
2020
Statut:
epublish
Résumé
The emergence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the etiological agent of the 2019 coronavirus disease (COVID-19), has erupted into a global pandemic that has led to tens of millions of infections and hundreds of thousands of deaths worldwide. The development of therapeutics to treat infection or as prophylactics to halt viral transmission and spread is urgently needed. SARS-CoV-2 relies on structural rearrangements within a spike (S) glycoprotein to mediate fusion of the viral and host cell membranes. Here, we describe the development of a lipopeptide that is derived from the C-terminal heptad repeat (HRC) domain of SARS-CoV-2 S that potently inhibits infection by SARS-CoV-2. The lipopeptide inhibits cell-cell fusion mediated by SARS-CoV-2 S and blocks infection by live SARS-CoV-2 in Vero E6 cell monolayers more effectively than previously described lipopeptides. The SARS-CoV-2 lipopeptide exhibits broad-spectrum activity by inhibiting cell-cell fusion mediated by SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV) and blocking infection by live MERS-CoV in cell monolayers. We also show that the SARS-CoV-2 HRC-derived lipopeptide potently blocks the spread of SARS-CoV-2 in human airway epithelial (HAE) cultures, an
Identifiants
pubmed: 33082259
pii: mBio.01935-20
doi: 10.1128/mBio.01935-20
pmc: PMC7587434
pii:
doi:
Substances chimiques
Antiviral Agents
0
Lipopeptides
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI114736
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM056414
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI146980
Pays : United States
Informations de copyright
Copyright © 2020 Outlaw et al.
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