Abstract
A novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has emerged as the causative agent behind the coronavirus disease 2019 (COVID-19) pandemic. Treatment efforts have been severely impeded due to the lack of specific effective antiviral drugs for the treatment of COVID-associated pathologies. In the present research endeavour the inhibitory prospects of cyanobacterial metabolites were assessed at the active binding pockets of the two vital SARS-CoV-2 proteases namely, main protease (M pro ) and the papain-like protease (PL pro ) that proteolytically process viral polyproteins and facilitate viral replication, employing an in silico molecular interaction-based approach. It was evident from our analysis based on the binding energy scores that the metabolites cylindrospermopsin, deoxycylindrospermopsin, carrageenan, cryptophycin 52, eucapsitrione, tjipanazole, tolyporphin and apratoxin A exhibited promising inhibitory potential against the SARS-CoV-2 M pro . The compounds cryptophycin 1, cryptophycin 52 and deoxycylindrospermopsin were observed to display encouraging binding energy scores with the PL pro of SARS-CoV-2. Subsequent estimation of physicochemical properties and potential toxicity of the metabolites followed by robust molecular dynamics simulations and analysis of MM-PBSA energy scoring function established deoxycylindrospermopsin as the most promising inhibitory candidate against both SARS-CoV-2 proteases. Present research findings bestow ample scopes to further exploit the potential of deoxycylindrospermopsin as a successful inhibitor of SARS-CoV-2 in vitro and in vivo and pave the foundation for the development of novel effective therapeutics against COVID-19.Communicated by Ramaswamy H. Sarma.
Keywords: MM-PBSA; SARS-CoV-2; cyanobacterial metabolites; deoxycylindrospermopsin; drug-likeness; molecular docking; molecular dynamics simulations.
【저자키워드】 SARS-CoV-2, molecular docking, molecular dynamics simulations, MM-PBSA, cyanobacterial metabolites, deoxycylindrospermopsin, drug-likeness, 【초록키워드】 COVID-19, Treatment, coronavirus disease, Coronavirus disease 2019, coronavirus, pandemic, antiviral drugs, molecular docking, Toxicity, molecular dynamics, protease, in vitro, in silico, molecular dynamics simulations, drug-likeness, antiviral drug, binding energy, Molecular dynamics simulation, Papain-like protease, Viral, viral replication, Research, carrageenan, Proteases, metabolites, molecular, respiratory, in vivo, inhibitor, Pathologies, metabolite, Analysis, Physicochemical properties, followed by, causative agent, acute respiratory syndrome, acute respiratory syndrome coronavirus, SARS-CoV-2 protease, Compound, M pro, foundation, effort, Papain, binding pocket, present, cryptophycin, cylindrospermopsin, inhibitory, polyprotein, approach, effective, robust, lack, facilitate, exhibited, physicochemical property, research finding, the SARS-CoV-2, were assessed, 【제목키워드】 in silico analysis, metabolite,