In Silico Analysis of Scopoletin Interaction with Potential SARS-CoV-2 Target

Abstract

SARS-CoV-2 virus belongs to the family Coronaviridae, genus Betacoronavirus that appeared in late 2019 in Wuhan, China caused the historically remembered pandemic of COVID-19 which is still not subsiding. The main protease, or Mpro, plays a key role in the expression and replication of viral genes and is therefore an extremely attractive target for the design of antiviral drugs against SARS-CoV-2. Numerous herbal components have been studied for their natural ability to be effective antiviral agents. Scopoletin (6-methoxy-7-hydroxycoumarin) is a coumarin compound with antimicrobial, anti-inflammatory, antioxidant, antitumor and hepatoprotective properties that has been isolated from several plant species (Scopolia japonica Maxim. - Japanese belladonna, Artemisia scoparia Waldst. & Kit. - wormwood and Viburnum prunifolium L. - black haw). The objectives of this study were to examine the interaction of scopoletin with the main protease Mpro SARS-CoV-2 and to determine its potential antiviral activity. The research covers the virtual interaction of scopoletin and main proteases Mpro of SARS-CoV-2 virus using AutoDock Vina version 1.1.2. The three-dimensional structure of the main protease Mpro of SARS-CoV-2 (PDB ID: 6Y84), taken from Protein Data Bank, and the scopoletin structure taken from the PubChem chemical database, which was used in SDF form and converted using the online software Online SMILES Translator and Structure File Generator in PDB 3D form, were used for analysis. The final result of the analysis was visualized using Pymol 2.4. As positive control of binding affinity and proven therapeutic effect, we used hydroxychloroquine. Our results point out that scopoletin has a potential to bind to and inhibit the SARS-CoV-2 3Clpro main protease similarly to hydroxychloroquine that have been proven as antiviral in previous preclinical and clinical studies. After successful docking analysis it was shown that scopoletin has a binding affinity for the main protease SARS-CoV-2 at −6.9 kcal/mol. This result indicates that scopoletin, as well as other coumarin derivatives, can potentially be used in the fight against COVID-19, but further in vitro and in vivo studies are certainly necessary.