In silico Study of Antiviral Activity of Polyphenol Compounds from Ocimum basilicum by Molecular Docking, ADMET, and Drug-Likeness Analysis.

Abstract

The SARS-CoV-2 virus is a disease that has mild to severe effects on patients, which can even lead to death. One of the enzymes that act as DNA replication is the main protease, which becomes the main target in the inhibition of the SARS-CoV-2 virus. In finding effective drugs against this virus, Ocimum basilicum is a potential herbal plant because it has been tested to have high phytochemical content and bioactivity. Apigenin-7-glucuronide, dihydrokaempferol-3-glucoside, and aesculetin are polyphenolic compounds found in Ocimum basilicum. The purpose of this study was to analyze the mechanism of inhibition of the three polyphenolic compounds in Ocimum basilicum against the main protease and to predict pharmacokinetic activity and the drug-likeness of a compound using the Lipinski Rule of Five. The method used is to predict the molecular docking inhibition mechanism using Autodock 4.0 tools and use pkcsm and protox online web server to analyze ADMET and Drug-likeness. The binding affinity for apigenin-7-glucuronide was -8.77 Kcal/mol, dihydrokaempferol-3-glucoside was -8.96 Kcal/mol, and aesculetin was -5.79 Kcal/mol. Then, the inhibition constant values were 375.81 nM, 270.09 nM, and 57.11 µM, respectively. Apigenin-7-glucuronide and dihydrokaempferol-3-glucoside bind to the main protease enzymes on the active sites of CYS145 and HIS41, while aesculetin only binds to the active sites of CYS145. On ADMET analysis, these three compounds met the predicted pharmacokinetic parameters, although there are some specific parameters that must be considered especially for aesculetin compounds. Meanwhile, on drug-likeness analysis, apigenin-7-glucuronide and dihydrokaempferol-3-glucoside compounds have one violation and aesculetin have no violation. Based on the data obtained, Apigenin-7-glucuronide and dihydrokaempferol-3-glucoside are compounds that have more potential to have an antiviral effect on the main protease enzyme than aesculetin. Based on pharmacokinetic parameters and drug-likeness, three compounds can be used as lead compounds for further research.