In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication.
Animals
Antiviral Agents
/ chemistry
Betacoronavirus
/ isolation & purification
COVID-19
Caco-2 Cells
Cell Survival
/ drug effects
Chlorocebus aethiops
Coronavirus Infections
/ pathology
Drug Approval
Drug Evaluation, Preclinical
Drug Repositioning
Humans
Pandemics
Pneumonia, Viral
/ pathology
SARS-CoV-2
Small Molecule Libraries
/ chemistry
Vero Cells
Virus Replication
/ drug effects
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
04 08 2020
04 08 2020
Historique:
received:
12
05
2020
accepted:
24
07
2020
entrez:
6
8
2020
pubmed:
6
8
2020
medline:
13
8
2020
Statut:
epublish
Résumé
A novel coronavirus, named SARS-CoV-2, emerged in 2019 in China and rapidly spread worldwide. As no approved therapeutics exists to treat COVID-19, the disease associated to SARS-Cov-2, there is an urgent need to propose molecules that could quickly enter into clinics. Repurposing of approved drugs is a strategy that can bypass the time-consuming stages of drug development. In this study, we screened the PRESTWICK CHEMICAL LIBRARY composed of 1,520 approved drugs in an infected cell-based assay. The robustness of the screen was assessed by the identification of drugs that already demonstrated in vitro antiviral effect against SARS-CoV-2. Thereby, 90 compounds were identified as positive hits from the screen and were grouped according to their chemical composition and their known therapeutic effect. Then EC50 and CC50 were determined for a subset of 15 compounds from a panel of 23 selected drugs covering the different groups. Eleven compounds such as macrolides antibiotics, proton pump inhibitors, antiarrhythmic agents or CNS drugs emerged showing antiviral potency with 2 < EC50 ≤ 20 µM. By providing new information on molecules inhibiting SARS-CoV-2 replication in vitro, this study provides information for the selection of drugs to be further validated in vivo. Disclaimer: This study corresponds to the early stages of antiviral development and the results do not support by themselves the use of the selected drugs to treat SARS-CoV-2 infection.
Identifiants
pubmed: 32753646
doi: 10.1038/s41598-020-70143-6
pii: 10.1038/s41598-020-70143-6
pmc: PMC7403393
doi:
Substances chimiques
Antiviral Agents
0
Small Molecule Libraries
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
13093Subventions
Organisme : H2020 Research Infrastructures
ID : 871029
Pays : International
Organisme : Institut National de la Santé et de la Recherche Médicale
ID : REACTing
Pays : International
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