期刊
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
卷 39, 期 16, 页码 6249-6264出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/07391102.2020.1796810
关键词
SARS-CoV-2 and RNA-dependent RNA polymerase (RdRp); molecular docking; molecular dynamics; MM-PBSA; natural polyphenols
资金
- Indian Institute of Technology Indore
- Indian Institute of Technology Palakkad
- Ministry of Human Resource Development, Govt. of India
- Department of Science and Technology-Science AMP
- Engineering Research Board (DST-SERB), Govt. of India [ECR/2017/002082]
- Department of Biotechnology, Govt. of India [BT/RLF/Re-entry/40/2014]
- DST-SERB, Govt. of India [ECR/2017/000010]
- DST, Govt. of India under the INSPIRE Fellowship Scheme [DST/INSPIRE Fellowship/2017/IF170145]
The sudden outbreak of COVID-19 has posed a massive threat to global public health. Research has shown that polyphenols can bind to the RNA replication enzyme of the novel coronavirus, potentially offering an effective treatment for COVID-19.
The sudden outburst of Coronavirus disease (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) poses a massive threat to global public health. Currently, no therapeutic drug or vaccine exists to treat COVID-19. Due to the time taking process of new drug development, drug repurposing might be the only viable solution to tackle COVID-19. RNA-dependent RNA polymerase (RdRp) catalyzes SARS-CoV-2 RNA replication and hence, is an obvious target for antiviral drug design. Interestingly, several plant-derived polyphenols effectively inhibit the RdRp of other RNA viruses. More importantly, polyphenols have been used as dietary supplementations for a long time and played beneficial roles in immune homeostasis. We were curious to study the binding of polyphenols with SARS-CoV-2 RdRp and assess their potential to treat COVID-19. Herein, we made a library of polyphenols that have shown substantial therapeutic effects against various diseases. They were successfully docked in the catalytic pocket of RdRp. The investigation reveals that EGCG, theaflavin (TF1), theaflavin-3'-O-gallate (TF2a), theaflavin-3'-gallate (TF2b), theaflavin 3,3'-digallate (TF3), hesperidin, quercetagetin, and myricetin strongly bind to the active site of RdRp. Further, a 150-ns molecular dynamic simulation revealed that EGCG, TF2a, TF2b, TF3 result in highly stable bound conformations with RdRp. The binding free energy components calculated by the MM-PBSA also confirm the stability of the complexes. We also performed a detailed analysis of ADME prediction, toxicity prediction, and target analysis for their druggability. Overall, our results suggest that EGCG, TF2a, TF2b, TF3 can inhibit RdRp and represent an effective therapy for COVID-19. Communicated by Ramaswamy H. Sarma
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