Identifying the natural polyphenol catechin as a multi-targeted agent against SARS-CoV-2 for the plausible therapy of COVID-19: an integrated computational approach

• Published in: Briefings in bioinformatics 2021-03, Vol.22 (2), p.1346-1360
• Main Authors: Mishra, Chandra Bhushan, Pandey, Preeti, Sharma, Ravi Datta, Malik, Md Zubbair, Mongre, Raj Kumar, Lynn, Andrew M, Prasad, Rajendra, Jeon, Raok, Prakash, Amresh
• Format: Article
• Language: English
• Subjects: ACE2; Angiotensin; Angiotensin-converting enzyme 2; Antiviral agents; Binding; Case Study; Catechin; Catechin - chemistry; Catechin - pharmacology; Catechin - therapeutic use; Cathepsin L; Chymotrypsin; Computer applications; Coronaviruses; COVID-19; COVID-19 - virology; COVID-19 Drug Treatment; Cysteine proteinase; Disease transmission; DNA-directed RNA polymerase; Drug development; Free energy; Glycoproteins; Humans; Hydrophobicity; Molecular Docking Simulation; Molecular dynamics; Molecular Dynamics Simulation; Molecular interactions; Nucleocapsids; Pandemics; Peptidyl-dipeptidase A; Polyphenols - pharmacology; Polyphenols - therapeutic use; Proteins; Respiratory diseases; RNA polymerase; RNA-directed RNA polymerase; SARS-CoV-2 - drug effects; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Vaccines; Viral diseases; Viruses
• ISSN: 1467-5463; 1477-4054
• DOI: 10.1093/bib/bbaa378

Abstract The global pandemic crisis, coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has claimed the lives of millions of people across the world. Development and testing of anti-SARS-CoV-2 drugs or vaccines have not turned to be realistic within the timeframe needed to combat this pandemic. Here, we report a comprehensive computational approach to identify the multi-targeted drug molecules against the SARS-CoV-2 proteins, whichare crucially involved in the viral–host interaction, replication of the virus inside the host, disease progression and transmission of coronavirus infection. Virtual screening of 75 FDA-approved potential antiviral drugs against the target proteins, spike (S) glycoprotein, human angiotensin-converting enzyme 2 (hACE2), 3-chymotrypsin-like cysteine protease (3CLpro), cathepsin L (CTSL), nucleocapsid protein, RNA-dependent RNA polymerase (RdRp) and non-structural protein 6 (NSP6), resulted in the selection of seven drugs which preferentially bind to the target proteins. Further, the molecular interactions determined by molecular dynamics simulation revealed that among the 75 drug molecules, catechin can effectively bind to 3CLpro, CTSL, RBD of S protein, NSP6 and nucleocapsid protein. It is more conveniently involved in key molecular interactions, showing binding free energy (ΔGbind) in the range of −5.09 kcal/mol (CTSL) to −26.09 kcal/mol (NSP6). At the binding pocket, catechin is majorly stabilized by the hydrophobic interactions, displays ΔEvdW values: −7.59 to −37.39 kcal/mol. Thus, the structural insights of better binding affinity and favorable molecular interaction of catechin toward multiple target proteins signify that catechin can be potentially explored as a multi-targeted agent against COVID-19. Graphical Abstract Graphical Abstract