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FDA-approved Pralatrexate identified by virtual drug screening inhibits SARS-CoV-2 replication in vitro

FDA-approved Pralatrexate identified by virtual drug screening inhibits SARS-CoV-2 replication in vitro

Authors :
Huiling Zhang
Yin Peng
Md. Tofazzal Hossain
Haiping Zhang
Yingxia Liu
Junxin Li
Yi Shi
Yanjie Wei
Min Wang
Justin Tze Yang Ng
Xiaochun Wan
Xiaohu Ren
Maoxuan Liu
Yang Yang
Konda Mani Saravanan
Yi Pan
Jinli Wei
Publication Year :
2020
Publisher :
Research Square Platform LLC, 2020.

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses serious threats to the global public health and leads to an unprecedented worldwide crisis. Unfortunately, no effective drugs or vaccines are available till now. Since the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is a promising therapeutic target, a deep learning and molecular simulation based hybrid drug screening procedure was proposed and applied to identify potential drug candidates targeting RdRp from 1906 approved drugs. Among the four selected FDA-approved 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 accurate virtual drug screening for inhibitors of SARS-CoV-2 and provides potential therapeutic agents against COVID-19.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........454d3f092afbf5d872edc4f0d9cf3ee8
Full Text :
https://doi.org/10.21203/rs.3.rs-36439/v2