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

13, April 2021 |

Authors:

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-isotheaavin-3-gallate and theaavin-3,3-digallate are effective proteinase (3CL pro ) inhibitors of SARS-CoV (IC50 < 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 anities in both systems in the following order: tannic acid > 3- isotheaavin-3-gallate > theaavin-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.