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Deprecated: Implicit conversion from float 284.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 J+Biomol+Struct+Dyn 2022 ; 40 (8): 3609-3625 Nephropedia Template TP
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Targeting SARS-CoV-2 main protease: structure based virtual screening, in silico ADMET studies and molecular dynamics simulation for identification of potential inhibitors #MMPMID33226303
Uniyal A; Mahapatra MK; Tiwari V; Sandhir R; Kumar R
J Biomol Struct Dyn 2022[May]; 40 (8): 3609-3625 PMID33226303show ga
COVID-19 pandemic has created a healthcare crisis across the world and has put human life under life-threatening circumstances. The recent discovery of the crystallized structure of the main protease (M(pro)) from SARS-CoV-2 has provided an opportunity for utilizing computational tools as an effective method for drug discovery. Targeting viral replication has remained an effective strategy for drug development. M(pro) of SARS-COV-2 is the key protein in viral replication as it is involved in the processing of polyproteins to various structural and nonstructural proteins. Thus, M(pro) represents a key target for the inhibition of viral replication specifically for SARS-CoV-2. We have used a virtual screening strategy by targeting M(pro) against a library of commercially available compounds to identify potential inhibitors. After initial identification of hits by molecular docking-based virtual screening further MM/GBSA, predictive ADME analysis, and molecular dynamics simulation were performed. The virtual screening resulted in the identification of twenty-five top scoring structurally diverse hits that have free energy of binding (DeltaG) values in the range of -26-06 (for compound AO-854/10413043) to -59.81 Kcal/mol (for compound 329/06315047). Moreover, the top-scoring hits have favorable AMDE properties as calculated using in silico algorithms. Additionally, the molecular dynamics simulation revealed the stable nature of protein-ligand interaction and provided information about the amino acid residues involved in binding. Overall, this study led to the identification of potential SARS-CoV-2 M(pro) hit compounds with favorable pharmacokinetic properties. We believe that the outcome of this study can help to develop novel M(pro) inhibitors to tackle this pandemic.Communicated by Ramaswamy H. Sarma.