In silico investigation of phytoconstituents from Indian medicinal herb ' Tinospora cordifolia (giloy)' against SARS-CoV-2 (COVID-19) by molecular dynamics approach

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 M^pro or 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, 3CL^pro is used to study drug:3CL^pro interactions and thus to investigate whether all or any of the main chemical constituents of Tinospora cordifolia (e.g. berberine (C₂₀H₁₈NO₄), β-sitosterol (C₂₉H₅₀O), coline (C₅H₁₄NO), tetrahydropalmatine (C₂₁H₂₅NO₄) and octacosanol (C₂₈H₅₈O)) 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 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. Communicated by Ramaswamy H. Sarma.

Keywords: Tinospora cordifolia; 3CLpro; COVID-19; SARS-CoV-2; berberine; β-sitosterol.