In Silico Investigation of Phytoconstituents from Indian Medicinal Herb 'Tinospora cordifolia (Giloy)' against SARS-CoV-2 (COVID-19) by Molecular Dynamics Approach

TL;DR

This study uses molecular dynamics and docking to investigate phytochemicals from Tinospora cordifolia as potential inhibitors of SARS-CoV-2 main protease, identifying berberine as a promising antiviral candidate.

Contribution

It provides the first in silico analysis of Tinospora cordifolia's constituents against COVID-19 main protease, highlighting berberine's potential as an antiviral agent.

Findings

Berberine shows strong binding affinity to 3CLpro.

Molecular dynamics confirms stable berberine-3CLpro interaction.

Berberine may inhibit viral replication by targeting 3CLpro.

Abstract

The recent appearance of COVID-19 virus has created a global crisis due to unavailability of any vaccine or drug that can effectively and deterministically work against it. Naturally, different possibilities (including herbal medicines having known therapeutic significance) have been explored by the scientists. The systematic scientific study (beginning with in silico study) of herbal medicines in particular and any drug in general is now possible as the structural components (proteins) of COVID-19 are already characterized. The main protease of COVID-19 virus is $\rm{M^{pro}}$ or $\rm{3CL^{pro}}$ which is a key CoV enzyme and an attractive drug target as it plays a pivotal role in mediating viral replication and transcription. In the present study, $\rm{3CL^{pro}}$ is used to study drug:3CLpro interactions and thus to investigate whether all or any of the main chemical constituents of Tinospora cordifolia (e.g., berberine $\rm{(C_{20}H_{18}NO_{4})}$, $\beta$-sitosterol $\rm{(C_{29}H_{50}O)}$, choline $\rm{(C_{5}H_{14}NO)}$, tetrahydropalmatine $\rm{(C_{21}H_{25}NO_{4})}$ and octacosanol $\rm{(C_{28}H_{58}O))}$ can be used as an anti-viral drug against SARS-CoV-2. The in silico study performed using tools of network pharmacology, molecular docking including molecular dynamics have revealed that among all considered phytochemicals in Tinospora cordifolia, berberine can regulate $\rm{3CL^{pro}}$ protein's function due to its easy inhibition and thus can control viral replication. The selection of Tinospora cordifolia was motivated by the fact that the main constituents of it are known to be responsible for various antiviral activities and the treatment of jaundice, rheumatism, diabetes, etc.