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Tytuł:
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A novel virtual screening procedure identifies Pralatrexate as inhibitor of SARS-CoV-2 RdRp and it reduces viral replication in vitro.
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Autorzy:
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Zhang H; Center for High Performance Computing, Joint Engineering Research Center for Health Big Data Intelligent Analysis Technology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China.
Yang Y; Shenzhen Key Laboratory of Pathogen and Immunity, National Clinical Research Center for infectious disease, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China.
Li J; Shenzhen Laboratory of Human Antibody Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, University City of Shenzhen, Shenzhen, China.
Wang M; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Saravanan KM; Center for High Performance Computing, Joint Engineering Research Center for Health Big Data Intelligent Analysis Technology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China.
Wei J; Shenzhen Key Laboratory of Pathogen and Immunity, National Clinical Research Center for infectious disease, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China.
Tze-Yang Ng J; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
Tofazzal Hossain M; Center for High Performance Computing, Joint Engineering Research Center for Health Big Data Intelligent Analysis Technology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China.; University of Chinese Academy of Sciences, Shijingshan District, Beijing, China.
Liu M; Shenzhen Laboratory of Human Antibody Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, University City of Shenzhen, Shenzhen, China.
Zhang H; Center for High Performance Computing, Joint Engineering Research Center for Health Big Data Intelligent Analysis Technology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China.
Ren X; Institute of Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
Pan Y; Department of Computer Science, Georgia State University, Atlanta, Georgia, United States of America.
Peng Y; Department of Pathology, School of Medicine, Shenzhen University, Shenzhen, China.
Shi Y; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Wan X; Shenzhen Laboratory of Human Antibody Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, University City of Shenzhen, Shenzhen, China.
Liu Y; Shenzhen Key Laboratory of Pathogen and Immunity, National Clinical Research Center for infectious disease, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China.
Wei Y; Center for High Performance Computing, Joint Engineering Research Center for Health Big Data Intelligent Analysis Technology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China.
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Źródło:
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PLoS computational biology [PLoS Comput Biol] 2020 Dec 31; Vol. 16 (12), pp. e1008489. Date of Electronic Publication: 2020 Dec 31 (Print Publication: 2020).
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: San Francisco, CA : Public Library of Science, [2005]-
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MeSH Terms:
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Drug Repositioning*
Aminopterin/*analogs & derivatives
Antiviral Agents/*pharmacology
Drug Evaluation, Preclinical/*methods
RNA-Dependent RNA Polymerase/*antagonists & inhibitors
SARS-CoV-2/*physiology
Aminopterin/chemistry ; Aminopterin/pharmacology ; Animals ; Azithromycin/chemistry ; Azithromycin/pharmacology ; Chlorocebus aethiops ; Computer Simulation ; Deep Learning ; Molecular Dynamics Simulation ; RNA-Dependent RNA Polymerase/chemistry ; Vero Cells ; Virus Replication/drug effects ; COVID-19 Drug Treatment
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Substance Nomenclature:
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0 (10-propargyl-10-deazaaminopterin)
0 (Antiviral Agents)
83905-01-5 (Azithromycin)
EC 2.7.7.48 (RNA-Dependent RNA Polymerase)
JYB41CTM2Q (Aminopterin)
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Entry Date(s):
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Date Created: 20201231 Date Completed: 20210108 Latest Revision: 20221207
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Update Code:
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20240105
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PubMed Central ID:
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PMC7774833
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DOI:
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10.1371/journal.pcbi.1008489
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PMID:
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33382685
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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.
Competing Interests: NO authors have competing interests
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