In silico study of potential SARS-CoV-2 antagonist from Clitoria ternatea

In this study, we implemented a structure-based virtual screening protocol in search of natural bioactive compounds in Clitoria ternatea that could inhibit the viral M^pro.

A library of twelve main bioactive compounds in C. ternatea was created from PubChem database by minimizing ligand structure in PyRx software to increase the ligand flexibility. Molecular docking studies were performed by targeting M^pro (PDB ID: 6lu7) via Discovery Studio Visualiser and PyRx platforms. Top hits compounds were then selected to study their Adsorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug likeness properties through pkCSM pharmacokinetics tool to understand the stability, interaction, conformational changes, and pharmaceutical relevant parameters.

This investigation found that, in the molecular docking simulation, four bioactive compounds (procyanidin A2 [-9.3 kcal/mol], quercetin-3-rutinoside [-8.9 kcal/mol], delphinidin-3-O-glucoside [-8.3 kcal/mol], and ellagic acid [-7.4 kcal/mol]) showed producing the strongest binding affinity to the M^pro of severe acute respiratory syndrome coronavirus 2, as compared to positive control (N3 inhibitor) (-7.5 kcal/mol). These binding energies were found to be favorable for an efficient docking and resultant. In addition, the stability of quercetin-3-rutinoside and ellagic acid is higher without any unfavorable bond. The ADMET and drug likeness of these two compounds were found that they are considered an effective and safe coronavirus disease 2019 (COVID-19) inhibitors through Lipinski's Rule, absorption, distribution, metabolism, and toxicity properties.

From these results, it was concluded that C. ternatea possess potential therapeutic properties against COVID-19.