Screening of Natural Product and Natural Product like Molecules against SARS–CoV–2 Main Protease Using Molecular Modeling Methods

Objective: To determine possible MPro enzyme inhibitors by using structure-based virtual screening methods, in the ZINC Biogenic Data Set containing natural products and natural product-like molecules.

Materials and Methods: QVina, an AutoDockVina derivative, was used in virtual screening operations, GROMACS in molecular dynamics studies and SwissAdme server in ADME (Absorption, Distribution, Metabolism, and Excretion) calculations. KNIME (Konstanz Information Miner) and ChemAxon software were used for filtering data and creating three-dimensional structures of the molecules.

Results: Seven out of totally screened 51535 natural products or natural products like molecules were identified as possible candidate to be used as SARS–CoV–2 Main Protease (MPro) enzyme inhibitors based on the results obtained from structure based virtual screening and ADME models.

Conclusion: Among the seven potent molecules, two of them (ZINC000604382012 and ZINC000514288074) were selected as candidate molecules for further studies according to the results obtained from g_mmpbsa simulations and synthetic accessibility models. In addition, a workflow has been established to identify novel or potent Mpro enzyme inhibitors.