A novel virtual screening procedure identifies Pralatrexate as inhibitor of SARS-CoV-2 RdRp and it reduces viral replication in vitro.
PLoS Comput Biol
; 16(12): e1008489, 2020 12.
Article
in English
| MEDLINE | ID: covidwho-1004405
ABSTRACT
The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus poses serious threats to the global public health and leads to worldwide crisis. No effective drug or vaccine is readily available. The viral RNA-dependent RNA polymerase (RdRp) is a promising therapeutic target. A hybrid drug screening procedure was proposed and applied to identify potential drug candidates targeting RdRp from 1906 approved drugs. Among the four selected market available drug candidates, Pralatrexate and Azithromycin were confirmed to effectively inhibit SARS-CoV-2 replication in vitro with EC50 values of 0.008µM and 9.453 µM, respectively. For the first time, our study discovered that Pralatrexate is able to potently inhibit SARS-CoV-2 replication with a stronger inhibitory activity than Remdesivir within the same experimental conditions. The paper demonstrates the feasibility of fast and accurate anti-viral drug screening for inhibitors of SARS-CoV-2 and provides potential therapeutic agents against COVID-19.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
RNA-Dependent RNA Polymerase
/
Drug Evaluation, Preclinical
/
Drug Repositioning
/
SARS-CoV-2
/
Aminopterin
Type of study:
Prognostic study
Topics:
Traditional medicine
/
Vaccines
Limits:
Animals
Language:
English
Journal:
PLoS Comput Biol
Journal subject:
Biology
/
Medical Informatics
Year:
2020
Document Type:
Article
Affiliation country:
Journal.pcbi.1008489
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