Elucidation of the inhibitory activity of plant-derived SARS-CoV inhibitors and their potential as SARS-CoV-2 inhibitors

Abstract

Due to the necessity of treating the SARS-CoV-2 infection, several drugs are now being tested as possible therapies. Although approved vaccines bring much hope, a vaccination program covering the entire global population will take a very long period, which makes the development of effective antiviral drugs an effective solution for the immediate treatment of this dangerous infection. Previous studies found that three natural compounds: tannic acid, 3-isothea avin-3-gallate and thea avin-3,3-digallate are effective proteinase (3CL pro ) inhibitors of SARS-CoV (IC 50 < 10 µM). Based on this information, and due to the high percentage of sequence identity of SARS-CoV and SARS-CoV-2 3CL pro , these three compounds could be candidate inhibitors of SARS-CoV-2 3CL pro . In this paper, we explore the structural and energetic features that guided the molecular recognition of these three compounds for dimeric SARS-CoV2 and SARS-CoV 3CL pro , the functional state of this enzyme, by using docking and MD simulations with the molecular mechanics-generalized-born surface area (MMGBSA) approach. Energetic analysis demonstrated that the three compounds reached favorable a nities in both systems in the following order: tannic acid > 3isothea avin-3-gallate > thea avin-3,3-digallate, a tendency that is in line with that which was experimentally reported between these ligands and SARS-CoV 3CL pro . Therefore, tannic acid may have clinical usefulness against COVID-19 by acting as a potent inhibitor of SARS-CoV-2 3CL pro .

Molecular interactions of tannic acid and matrix metalloproteinases 2 and 9

“…The PDB files of TA, MMP-2, and MMP-9 were converted to PDBQT files by AutoDockTool 1.5.7 [38] . For TA, Gasteiger partial charges were added [39] . For MMP-2 and MMP-9, water and ligands were removed [40] , polar hydrogens were added, and Kollman charges were assigned [39] .…”

“…For TA, Gasteiger partial charges were added [39] . For MMP-2 and MMP-9, water and ligands were removed [40] , polar hydrogens were added, and Kollman charges were assigned [39] .…”

Molecular insights into the inhibition mechanism of harringtonine against essential proteins associated with SARS-CoV-2 entry

“…The binding free energies ( ΔG bind ) were evaluated by the molecular mechanics generalized Born surface area (MM/GBSA) approach in AmberTools18 [33] , [40] , which has been successfully used to predict the binding affinities for a variety of ligand-protein and protein-protein interactions [41] , [42] , [43] , [44] , [45] , [46] .…”