The SARS-CoV-2 helicase Nsp13 is a promising target for developing anti-COVID drugs. In the present study, we have identified potential natural product inhibitors of SARS-CoV-2 Nsp13 targeting the ATP-binding site using molecular docking and molecular dynamics (MD) simulations. MD simulation of the prepared crystal structure of SARS-CoV-2 Nsp13 was performed to generate an ensemble of structures of helicase Nsp13 capturing the conformational diversity of the ATP-binding site. A natural product library of more than 14,000 phytochemicals from Indian medicinal plants was used to perform virtual screening against the ensemble of Nsp13 structures. Subsequently, a two-stage filter, first based on protein–ligand docking binding energy value and second based on protein residues in the ligand-binding site and non-covalent interactions between the protein residues and the ligand in the best-docked pose, was used to identify 368 phytochemicals as potential inhibitors of SARS-CoV-2 helicase Nsp13. MD simulations of the top inhibitors complexed with protein were performed to confirm stable binding, and to compute MM-PBSA based binding energy. From among the 368 potential phytochemical inhibitors, the top identified potential inhibitors of SARS-CoV-2 helicase Nsp13 namely, Picrasidine M, (+)-Epiexcelsin, Isorhoeadine, Euphorbetin and Picrasidine N, can be taken up initially for experimental studies.
Graphic abstract
Supplementary Information
The online version contains supplementary material available at 10.1007/s11030-021-10251-1.
Keywords: COVID-19, SARS-CoV-2 helicase Nsp13, Phytochemical inhibitors, Molecular docking, Molecular dynamics simulation, Lead compounds
Author Biographies
R Vivek-Ananth, The Institute of Mathematical Sciences (IMSc), Chennai, 600113 India
Homi Bhabha National Institute (HBNI), Mumbai, 400094 India
Areejit Samal, The Institute of Mathematical Sciences (IMSc), Chennai, 600113 India
Homi Bhabha National Institute (HBNI), Mumbai, 400094 India
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