A novel virtual screening procedure identifies Pralatrexate as inhibitor of SARS-CoV-2 RdRp and it reduces viral replication in vitro

doi:10.1371/journal.pcbi.1008489

	A novel virtual screening procedure identifies Pralatrexate as inhibitor of SARS-CoV-2 RdRp and it reduces viral replication in vitro
	Zhang, Haiping 3; Yang, Yang 5; Li, Junxin 6; Wang, Min 7; Saravanan, Konda Mani 3; Wei, Jinli 5; Ng, Justin Tze-Yang 8; Hossain, Md Tofazzal 3,9; Liu, Maoxuan 6; Zhang, Huiling 3
刊名	PLOS COMPUTATIONAL BIOLOGY
	2020-12-01
卷号	16 期号:12 页码:20
ISSN号	1553-734X
DOI	10.1371/journal.pcbi.1008489
英文摘要	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 0.008 mu M and 9.453 mu M, 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. Author summary Currently, a novel coronavirus called SARS-COV-2 is spreading across many parts of the world. Unfortunately, there is still a lack of effective drugs against the virus. Additionally, it usually takes much longer time to develop a new drug using traditional methods. Thus, it is now better to rely on some alternative methods to develop drugs that can treat such a disease effectively. In this paper, we have proposed a deep learning and molecular dynamics simulation based hybrid drug screening procedure for identifying potential drug candidates targeting RdRp from 1906 market available drugs. Our screening have successfully identified a FDA-approved drug called Pralatrexate that strongly inhibits the replication of 2019-nCoV in vitro with EC50 values of 0.008 mu M. This work demonstrated the feasibility of accurate virtual drug screening for inhibitors of SARS-CoV-2 and provides potential therapeutic agents against COVID-19.
资助项目	National Key Research and Development Program of China[2018YFB0204403] ; National Key Research and Development Program of China[2019YFA0906100] ; National Science and Technology Major Project[2018ZX10101004] ; National Science Foundation of China[U1813203] ; National Natural Youth Science Foundation of China[31601028] ; Shenzhen Basic Research Fund[JCYJ20190807170801656] ; Shenzhen Basic Research Fund[JCYJ20180507182818013] ; Shenzhen Basic Research Fund[JCYJ20170413093358429] ; SIAT Innovation Program for Excellent Young Researchers ; Strategic Priority CAS Project[XDB38000000]
WOS研究方向	Biochemistry & Molecular Biology ; Mathematical & Computational Biology
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000605330800002
内容类型	期刊论文
源URL	[http://119.78.100.204/handle/2XEOYT63/16379]
专题	中国科学院计算技术研究所
通讯作者	Wan, Xiaochun; Liu, Yingxia; Wei, Yanjie
作者单位	1.Georgia State Univ, Dept Comp Sci, Atlanta, GA 30303 USA 2.Shenzhen Ctr Dis Control & Prevent, Inst Toxicol, Shenzhen, Peoples R China 3.Chinese Acad Sci, Ctr High Performance Comp, Joint Engn Res Ctr Hlth Big Data Intelligent Anal, Shenzhen Inst Adv Technol, Shenzhen, Guangdong, Peoples R China 4.Shenzhen Univ, Sch Med, Dept Pathol, Shenzhen, Peoples R China 5.Southern Univ Sci & Technol, Hosp Affiliated 1, Shenzhen Peoples Hosp 3,Shenzhen Key Lab Pathogen, State Key Discipline Infect Dis,Natl Clin Res Ctr, Shenzhen, Peoples R China 6.Chinese Acad Sci, Univ City Shenzhen, Inst Biomed & Biotechnol, Shenzhen Inst Adv Technol,Shenzhen Lab Human Anti, Shenzhen, Peoples R China 7.Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China 8.Nanyang Technol Univ, Sch Biol Sci, Singapore, Singapore 9.Univ Chinese Acad Sci, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Haiping,Yang, Yang,Li, Junxin,et al. A novel virtual screening procedure identifies Pralatrexate as inhibitor of SARS-CoV-2 RdRp and it reduces viral replication in vitro[J]. PLOS COMPUTATIONAL BIOLOGY,2020,16(12):20.
APA	Zhang, Haiping.,Yang, Yang.,Li, Junxin.,Wang, Min.,Saravanan, Konda Mani.,...&Wei, Yanjie.(2020).A novel virtual screening procedure identifies Pralatrexate as inhibitor of SARS-CoV-2 RdRp and it reduces viral replication in vitro.PLOS COMPUTATIONAL BIOLOGY,16(12),20.
MLA	Zhang, Haiping,et al."A novel virtual screening procedure identifies Pralatrexate as inhibitor of SARS-CoV-2 RdRp and it reduces viral replication in vitro".PLOS COMPUTATIONAL BIOLOGY 16.12(2020):20.