The potential chemical structure of anti‐SARS‐CoV‐2 RNA‐dependent RNA polymerase

• Published in: Journal of Medical Virology Vol. 92; no. 6; pp. 693 - 697
• Main Authors: Lung, Jrhau, Lin, Yu‐Shih, Yang, Yao‐Hsu, Chou, Yu‐Lun, Shu, Li‐Hsin, Cheng, Yu‐Ching, Liu, Hung Te, Wu, Ching‐Yuan
• Format: Journal Article Web Resource
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.06.2020; John Wiley & Sons, Inc; John Wiley and Sons Inc
• Subjects: Amino Acid Sequence; Antiviral activity; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Betacoronavirus - drug effects; Betacoronavirus - enzymology; Betacoronavirus - genetics; Biflavonoids - chemistry; Biflavonoids - pharmacology; Binding energy; Catalytic Domain; Catechin - chemistry; Catechin - pharmacology; Computational Biology - methods; Coronaviridae; Coronaviruses; COVID-19; DNA-directed RNA polymerase; Docks; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - pharmacology; Gene Expression; Humans; Hydrogen Bonding; Hydrogen bonds; Hydrophobic and Hydrophilic Interactions; Hydrophobicity; Inhibitors; Middle East respiratory syndrome; Middle East Respiratory Syndrome Coronavirus - drug effects; Middle East Respiratory Syndrome Coronavirus - enzymology; Middle East Respiratory Syndrome Coronavirus - genetics; Molecular docking; Molecular Docking Simulation; Protein Binding; Protein Interaction Domains and Motifs; Protein Structure, Secondary; Respiratory diseases; RNA polymerase; RNA-Dependent RNA Polymerase - antagonists & inhibitors; RNA-Dependent RNA Polymerase - chemistry; RNA-Dependent RNA Polymerase - genetics; RNA-Dependent RNA Polymerase - metabolism; RNA‐dependent RNA polymerase; SARS Virus - drug effects; SARS Virus - enzymology; SARS Virus - genetics; SARS-CoV-2; Sequence Alignment; Sequence Homology, Amino Acid; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Short Communication; Short Communications; theaflavin; Therapeutic applications; Thermodynamics; traditional Chinese medicinal compounds; Viral diseases; Viral Proteins - antagonists & inhibitors; Viral Proteins - chemistry; Viral Proteins - genetics; Viral Proteins - metabolism; Virology; SARS-CoV-2; theaflavin; RNA-dependent RNA polymerase; traditional Chinese medicinal compounds
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.25761

An outbreak of coronavirus disease 2019 (COVID‐19) occurred in Wuhan and it has rapidly spread to almost all parts of the world. For coronaviruses, RNA‐dependent RNA polymerase (RdRp) is an important protease that catalyzes the replication of RNA from RNA template and is an attractive therapeutic target. In this study, we screened these chemical structures from traditional Chinese medicinal compounds proven to show antiviral activity in severe acute respiratory syndrome coronavirus (SARS‐CoV) and the similar chemical structures through a molecular docking study to target RdRp of SARS‐CoV‐2, SARS‐CoV, and Middle East respiratory syndrome coronavirus (MERS‐CoV). We found that theaflavin has a lower idock score in the catalytic pocket of RdRp in SARS‐CoV‐2 (−9.11 kcal/mol), SARS‐CoV (−8.03 kcal/mol), and MERS‐CoV (−8.26 kcal/mol) from idock. To confirm the result, we discovered that theaflavin has lower binding energy of −8.8 kcal/mol when it docks in the catalytic pocket of SARS‐CoV‐2 RdRp by using the Blind Docking server. Regarding contact modes, hydrophobic interactions contribute significantly in binding and additional hydrogen bonds were found between theaflavin and RdRp. Moreover, one π‐cation interaction was formed between theaflavin and Arg553 from the Blind Docking server. Our results suggest that theaflavin could be a potential SARS‐CoV‐2 RdRp inhibitor for further study. Highlights Theaflavin has a lower idock score in the catalytic pocket of RdRp in SARS‐CoV‐2, SARS‐CoV and MERS‐CoV from idock. Theaflavin has a lowest binding energy when it docks in the catalytic pocket of SARS‐CoV‐2 RdRp. Theaflavin could be potential SARS‐CoV‐2 RdRp inhibitor.