In silico screening of phenylethanoid glycosides, a class of pharmacologically active compounds as natural inhibitors of SARS-CoV-2 proteases

Abstract

Since the advent of Covid-19, several natural products have been investigated regarding their <i>in silico</i> interactions with SARS-CoV-2 proteases - 3CL^pro and PL^pro, two of the most important pharmacological targets for antiviral development. Phenylethanoid glycosides (PG) are a class of natural products present in important medicinal plants and a drug containing this group of active ingredients has been successfully used in the treatment of Covid-19 in China. Thus, a dataset with 567 derivatives of this class was built from reviews published between 1994 and 2020, and their interaction against both SARS-CoV-2 proteases was investigated. The virtual screening was performed by filtering the PGs through the evaluation of scores based on the AutoDock Vina, GOLD/ChemPLP, and GOLD/GoldScore evaluation functions. The bRO5 pharmacokinetic parameters of the PGs ranked in the previous step were analyzed and their interaction with key amino acid residues of the 3CL^pro and PL^pro enzymes was evaluated. Ninety-eight compounds were identified by computational approaches against PL^pro and 80 PGs against 3CL^pro. Of these, four interacted with key catalytic residues of PL^pro, which is an indicative of inhibitory activity, and three compounds interacted with catalytic key residues of 3CL^pro. Of these, five PGs occur in plants of the Traditional Chinese Medicine (TCM), while two are components of plants/formulations currently used in the Covid-19 protocols in China. The data presented here show the potential of PGs as selective inhibitors of SARS-CoV-2 3CL^pro and PL^pro.