tetano
Editor, Senior Moderator
Brief Bioinform
. 2020 Dec 31;bbaa378.
doi: 10.1093/bib/bbaa378. Online ahead of print.
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
Chandra Bhushan Mishra[SUP] 1 [/SUP], Preeti Pandey[SUP] 2 [/SUP], Ravi Datta Sharma[SUP] 3 [/SUP], Md Zubbair Malik[SUP] 4 [/SUP], Raj Kumar Mongre[SUP] 1 [/SUP], Andrew M Lynn[SUP] 5 [/SUP], Rajendra Prasad[SUP] 6 [/SUP], Raok Jeon[SUP] 1 [/SUP], Amresh Prakash[SUP] 7 [/SUP]
Affiliations
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.
Keywords: COVID-19; SARS-CoV-2; catechin; free energy landscape; multi-targeted drug.
. 2020 Dec 31;bbaa378.
doi: 10.1093/bib/bbaa378. Online ahead of print.
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
Chandra Bhushan Mishra[SUP] 1 [/SUP], Preeti Pandey[SUP] 2 [/SUP], Ravi Datta Sharma[SUP] 3 [/SUP], Md Zubbair Malik[SUP] 4 [/SUP], Raj Kumar Mongre[SUP] 1 [/SUP], Andrew M Lynn[SUP] 5 [/SUP], Rajendra Prasad[SUP] 6 [/SUP], Raok Jeon[SUP] 1 [/SUP], Amresh Prakash[SUP] 7 [/SUP]
Affiliations
- PMID: 33386025
- 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.
Keywords: COVID-19; SARS-CoV-2; catechin; free energy landscape; multi-targeted drug.