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.
【저자키워드】 COVID-19, SARS-CoV-2, free energy landscape, catechin, multi-targeted drug., 【초록키워드】 coronavirus disease, Coronavirus infection, Coronavirus disease 2019, Vaccine, coronavirus, pandemic, S protein, antiviral drugs, Transmission, Virtual screening, Proteins, drug, 3CLpro, molecular dynamics, severe acute respiratory syndrome Coronavirus, virus, binding free energy, anti-SARS-CoV-2, binding affinity, antiviral drug, hACE2, nucleocapsid protein, Molecular dynamics simulation, free energy, CTSL, Replication, global pandemic, Disease progression, RBD, free energy landscape, non-structural protein, RdRP, RNA-dependent RNA polymerase, glycoprotein, molecular, catechin, development, interactions, Human angiotensin-converting enzyme 2, NSP6, angiotensin, SARS-CoV-2 proteins, cysteine, determined by, cathepsin L, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, enzyme, cysteine protease, human Angiotensin-converting enzyme, chymotrypsin, binding pocket, hydrophobic, target proteins, molecular interaction, hydrophobic interactions, viral-host interaction, target protein, Host, approach, Seven, identify, caused, involved, claimed, the SARS-CoV-2, 【제목키워드】 therapy, identifying, approach,