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

• Published in: PLoS computational biology Vol. 16; no. 12; p. e1008489
• Main Authors: Zhang, Haiping, Yang, Yang, Li, Junxin, Wang, Min, Saravanan, Konda Mani, Wei, Jinli, Tze-Yang Ng, Justin, Tofazzal Hossain, Md, Liu, Maoxuan, Zhang, Huiling, Ren, Xiaohu, Pan, Yi, Peng, Yin, Shi, Yi, Wan, Xiaochun, Liu, Yingxia, Wei, Yanjie
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.12.2020; Public Library of Science (PLoS)
• Subjects: Acute lymphatic leukemia; Acute lymphoblastic leukemia; Adenosine; Aminopterin - analogs & derivatives; Aminopterin - chemistry; Aminopterin - pharmacology; Amoxicillin; Animals; Antibiotics; Antiviral Agents - pharmacology; Azithromycin; Azithromycin - chemistry; Azithromycin - pharmacology; Binding sites; Biology and life sciences; China; Chlorocebus aethiops; Computer Simulation; Control; Coordination numbers; Coronaviruses; COVID-19; COVID-19 - drug therapy; Deep Learning; Drug discovery; Drug Evaluation, Preclinical - methods; Drug Repositioning; Drugs; Epidemics; Free energy; Hepatitis; Hepatitis C; Hepatitis C virus; Hydrogen bonds; Inhibitors; Innovations; Leukemia; Libraries; Ligands; Liver diseases; Medicine and health sciences; Methods; Molecular Dynamics Simulation; Molecular weight; Nucleotide analogs; Nucleotides; Penicillin; Physical Sciences; Proteins; Replication; Research and Analysis Methods; RNA polymerase; RNA-Dependent RNA Polymerase - antagonists & inhibitors; RNA-Dependent RNA Polymerase - chemistry; RNA-directed RNA polymerase; SARS-CoV-2 - physiology; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Simulation; Technology application; Vero Cells; Viral diseases; Virus Replication - drug effects; Viruses; China

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 hybr...