Abstract

 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.
Highlights
The SARS-CoV-2 (COVID-19) outbreak emerged in Wuhan, China, towards the end of 2019 and soon turned into a pandemic
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
Docking simulations were performed on TRUBA servers with QVina 2.1, a derivative of AutoDockVina. [22, 23] The coordinates of the binding site were determined with the aid of the inhibitor N3 in the pdb file coded as 6LU7
Summary
The SARS-CoV-2 (COVID-19) outbreak emerged in Wuhan, China, towards the end of 2019 and soon turned into a pandemic. [1] Significant progress has been made in developing vaccines to prevent the infection of SARS-CoV-2 and mass vaccination studies have started in some countries. [2] Multiple approaches are being evaluated in the treatment of the virus, and studies are still ongoing. Antibodies, peptides, proteins and small molecules can be used to block the entry of the virus into the cell. Proteases such as RNA-dependent RNA polymerase (RdRp), papain-like cysteine protease (PLpro) or main protease (MPro) can be targeted to circumvent the virus replication. Choy et al studied the inhibition of the replication of SARS-CoV-2 in Vero-E6 cells with pro
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