Open AccessA novel virtual screening procedure identifies Pralatrexate as inhibitor of SARS-CoV-2 RdRp and it reduces viral replication in vitro
Author(s) -
Haiping Zhang,
Yang Yang,
Junxin Li,
Min Wang,
Konda Mani Saravanan,
Jinli Wei,
Jiawei Ng,
Tofazzal Hossain,
Maoxuan Liu,
Huiling Zhang,
Xiaohu Ren,
Yi Pan,
Pengfei Yin,
Yi Shi,
Xiaochun Wan,
Yingxia Liu,
Yanjie Wei
Publication year - 2020
Publication title -
plos computational biology/plos computational biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.628
H-Index - 182
eISSN - 1553-7358
pISSN - 1553-734X
DOI - 10.1371/journal.pcbi.1008489
Subject(s) - drug repositioning , viral replication , drug , coronavirus , virtual screening , virology , rna dependent rna polymerase , azithromycin , pharmacology , biology , drug discovery , computational biology , virus , covid-19 , medicine , polymerase , bioinformatics , microbiology and biotechnology , gene , antibiotics , genetics , disease , pathology , infectious disease (medical specialty)
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 EC 50 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.