Compounds Isolated from Lawsonia inermis L. Collected in Vietnam and Evaluation of Their Potential Activity Against the Main Protease of SARS-CoV-2 Using In silico Molecular Docking and Molecular Dynamic Simulation

Abstract

Since late 2019 to early 2020, an outbreak caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has become a worldwide health emergency due to its rapid infection and mortality of millions of people around the world. As the main protease Mpro or 3CLpro produced by the virus plays an important role in coronavirus survival and proliferation, it becomes an excellent drug target to identify COVID-19 inhibitors. Lawsonia inermis L. (henna) is a medicinal plant that has been used for a long time for the treatment of many fungal and bacterial infections. In the search for new anti-COVID agents from medicinal plants, we report the results of our study into the potential inhibition of Mpro by the compounds isolated from the extracts of L. inermis roots and leaves using molecular docking and molecular dynamics simulation. The molecular modeling results showed that all isolated compounds bonded spontaneously into the catalytic pockets of Mpro with binding energies <0. The docking and calculated pharmacokinetic results of the compounds (1-3, 6-8) were similar to and even better than those of the commercial COVID-19 inhibitor remdesivir. In particular, the triterpenoid glycoside suavissimoside R1 (8) showed the best binding to SARS-CoV Mpro, with the lowest binding energy ΔG and IC50,calc. values of −8.19 kcal/mol and 0.98 μM, respectively. Furthermore, the calculations of ADMET (absorption, distribution, metabolism, excretion, and toxicity) showed that it had the lowest toxicity, with a predicted LD50 value of 3320 mg/kg. These triterpenoids are worthy of further study to evaluate their actual bioactivity against SARS-CoV-2 in vitro and in vivo in the hope of contributing valuable scientific data for natural resources for the development novel drug formulations for either the prevention or treatment of COVID-19.