Molecular interactions of some phenolics with 2019-nCoV and related pathway elements

Abstract

As of June 2021, the novel coronavirus disease (SARS-CoV-2) resulted in 180 million cases worldwide and resulted in the death of approximately 4 million people. However, an effective pharmaceutical with low side effects that can be used in the treatment of SARS-CoV-2 infection has not been developed yet. The aim of this computational study was to analyze the interactions of twenty-two hydroxycinnamic acid and hydroxybenzoic acid derivatives with the SARS-CoV-2 receptor binding domain (RBD) and host organism's proteases, transmembrane serine protease 2 (TMPRSS2), and cathepsin B and L (CatB/L). According to the RBCI analysis, the ligands with the highest affinity against 4 enzymes in the molecular docking study were determined as 1-caffeoyl-β-D-glucose, rosmarinic acid, 3-p-coumaroylquinic acid and chlorogenic acid. It has also been observed that these compounds interacted more strongly with spike RBD, CatB and CatL enzymes. Although the top-ranked ligand, 1-caffeoyl-β-D-glucose, violated the drug-likeness criteria at 1 point (NH or OH>5) and ADMET in terms of AMES toxicity, the second top-ranked ligand rosmarinic acid neither violated drug-likeness nor exhibited incompatibility in terms of ADMET. In conclusion, with its anti-inflammatory properties, rosmarinic acid can be considered and further investigated as a plant-based pharmaceutical that can offer a treatment option in SARS-CoV-2 infection. However, our findings should be supported by additional in vitro and in vivo studies. © 2008 Universidade Federal do Rio Grande do Sul. All rights reserved.