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submitted on 03.08.2020 and posted on 04.08.2020by Chandra Bhushan Mishra, Preeti Pandey, Ravi Datta Sharma, Raj Kumar Mongre, Andrew M Lynn, Rajendra Prasad, Raok Jeon, Amresh Prakash
The global pandemic crisis, COVID-19 caused by 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, are not turned to be realistic in the timeframe
needed to combat this pandemic. Thus, rigorous efforts are still ongoing for the drug repurposing
as a clinical treatment strategy to control COVID-19. Here we report a comprehensive
computational approach to identify the multi-targeted drug molecules against the SARS-CoV-2
proteins, which are crucially involved in the viral-host interaction, replication of the virus inside
the host, disease progression and transmission of coronavirus infection. Virtual screening of 72
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, Nucleocapsid protein, RNA-dependent RNA polymerase (RdRp) and nonstructural protein 6 (NSP6) resulted in the selection of seven drugs which preferentially binds
to the target proteins. Further, the molecular interactions determined by MD simulation, free
energy landscape and the binding free energy estimation, using MM-PBSA revealed that
among 72 drug molecules, catechin (flavan-3-ol) can effectively bind to 3CLpro, Cathepsin L,
RBD of S protein, NSP-6, 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
(Cathepsin L) 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 favourable molecular interaction of catechin
towards multiple target proteins, signifies that catechin can be potentially explored as a multitargeted agent in the rational design of effective therapies against COVID-19.