A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease.
PLoS One
; 16(2): e0245962, 2021.
Article
in English
| MEDLINE | ID: covidwho-1058307
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
Effective SARS-CoV-2 antiviral drugs are desperately needed. The SARS-CoV-2 main protease (Mpro) appears as an attractive target for drug development. We show that the existing pharmacopeia contains many drugs with potential for therapeutic repurposing as selective and potent inhibitors of SARS-CoV-2 Mpro. We screened a collection of ~6,070 drugs with a previous history of use in humans for compounds that inhibit the activity of Mpro in vitro and found ~50 compounds with activity against Mpro. Subsequent dose validation studies demonstrated 8 dose responsive hits with an IC50 ≤ 50 µM. Hits from our screen are enriched with hepatitis C NS3/4A protease targeting drugs including boceprevir, ciluprevir. narlaprevir, and telaprevir. This work suggests previous large-scale commercial drug development initiatives targeting hepatitis C NS3/4A viral protease should be revisited because some previous lead compounds may be more potent against SARS-CoV-2 Mpro than boceprevir and suitable for rapid repurposing.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Protease Inhibitors
/
Hepatitis C
/
Hepacivirus
/
Drug Evaluation, Preclinical
/
Drug Repositioning
/
SARS-CoV-2
Type of study:
Prognostic study
Topics:
Traditional medicine
Limits:
Humans
Language:
English
Journal:
PLoS One
Journal subject:
Science
/
Medicine
Year:
2021
Document Type:
Article
Affiliation country:
Journal.pone.0245962
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