The rocaglate CR-31-B (-) inhibits SARS-CoV-2 replication at non-cytotoxic, low nanomolar concentrations in vitro and ex vivo.
Animals
Antiviral Agents
/ chemistry
Benzofurans
/ chemistry
Bronchi
/ virology
Cells, Cultured
Chlorocebus aethiops
Eukaryotic Initiation Factor-4A
/ antagonists & inhibitors
Humans
Hydroxamic Acids
/ chemistry
Respiratory Mucosa
/ virology
SARS-CoV-2
/ drug effects
Vero Cells
Viral Load
/ drug effects
Viral Replication Compartments
/ drug effects
Virus Replication
/ drug effects
Antiviral activity
COVID-19
Rocaglate
SARS-CoV-2
Translation initiation
eIF4A
Journal
Antiviral research
ISSN: 1872-9096
Titre abrégé: Antiviral Res
Pays: Netherlands
ID NLM: 8109699
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
05
10
2020
revised:
28
12
2020
accepted:
04
01
2021
pubmed:
11
1
2021
medline:
18
2
2021
entrez:
10
1
2021
Statut:
ppublish
Résumé
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19, a severe respiratory disease with varying clinical presentations and outcomes, and responsible for a major pandemic that started in early 2020. With no vaccines or effective antiviral treatments available, the quest for novel therapeutic solutions remains an urgent priority. Rocaglates, a class of plant-derived cyclopenta[b]benzofurans, exhibit broad-spectrum antiviral activity against multiple RNA viruses including coronaviruses. Specifically, rocaglates inhibit eukaryotic initiation factor 4A (eIF4A)-dependent mRNA translation initiation, resulting in strongly reduced viral RNA translation. Here, we assessed the antiviral activity of the synthetic rocaglate CR-31-B (-) against SARS-CoV-2 using both in vitro and ex vivo cell culture models. In Vero E6 cells, CR-31-B (-) inhibited SARS-CoV-2 replication with an EC
Identifiants
pubmed: 33422611
pii: S0166-3542(21)00002-4
doi: 10.1016/j.antiviral.2021.105012
pmc: PMC7791309
pii:
doi:
Substances chimiques
Antiviral Agents
0
Benzofurans
0
Hydroxamic Acids
0
N-methoxy rocaglamide
0
Eukaryotic Initiation Factor-4A
EC 2.7.7.-
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
Pagination
105012Subventions
Organisme : NCI NIH HHS
ID : R01 CA183876
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA192937
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA217694
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA207217
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA087486
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA252982
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.