Screening of phytochemical compounds of Tinospora cordifolia for their inhibitory activity on SARS-CoV-2: an in silico study

Abstract

In the present study, we explored phytochemical constituents of Tinospora cordifolia in terms of its binding affinity targeting the active site pocket of the main protease (3CL pro) of SARS-CoV-2 using molecular docking study and assessed the stability of top docking complex of tinosponone and 3CL pro using molecular dynamics simulations with GROMACS 2020.2 version. Out of 11 curated screened compounds, we found the significant docking score for tinosponone, xanosporic acid, cardiofolioside B, tembetarine and berberine in Tinospora cordifolia. Based on the findings of the docking study, it was confirmed that tinosponone is the potent inhibitor of main protease of SARS-CoV-2 with the best binding affinity of À7.7 kcal/mol. Further, ADME along with toxicity analysis was studied to predict the pharmacokinetics and drug-likeness properties of five top hits compounds. The molecular dynamics simulation analysis confirmed the stability of tinosponone and 3CL pro complex with a random mean square deviation (RMSD) value of 0.1 nm. The computer-aided drug design approach proved that the compound tinosponone from T. cordifolia is a potent inhibitor of 3CL main protease of SARS-CoV-2. Further, the in vitro and in vivo-based testing will be required to confirm its inhibitory effect on SARS-CoV-2.

Application of Humanized Zebrafish Model in the Suppression of SARS-CoV-2 Spike Protein Induced Pathology by Tri-Herbal Medicine Coronil via Cytokine Modulation

“…In line with our studies, molecular docking studies on T. cordifolia phyto-constituents to target the active site pocket of the 3CL pro , the main protease of SARS-CoV-2, identified that tinosponone, xanosporic acid, cardiofolioside, tembetarine, and berberine dock significantly to the 3CL pro protease [67]. Further in silico studies have also confirmed that tinocordioside and berberine present in T. cordifolia may also regulate SARS-CoV-2 entry and its replication [68,69].…”

Current Updates on Naturally Occurring Compounds Recognizing SARS-CoV-2 Druggable Targets

“…These findings agree with other studies [ 106 , 107 ]. An in silico study reported that berberine well-recognized the main protease by establishing hydrogen bond interactions with Phe140 and Asn142 [ 108 ].…”

Identification of Small Molecule Inhibitors of the Deubiquitinating Activity of the SARS-CoV-2 Papain-Like Protease: in silico Molecular Docking Studies and in vitro Enzymatic Activity Assay

“…The structures of the hits identified from these computational studies could be optimized as part of the drug discovery process (Ojha et al, 2020 ). In addition to synthetic pharmacological compounds, herbal constituents can be screened in the same manner and this method has been described in many papers (Bhowmik et al, 2020 ; Chikhale et al, 2020 ; Ghosh et al, 2020 ; Gupta et al, 2020 ; Jena et al, 2020 ; Krupanidhi et al, 2020 ; Muhseen et al, 2020 ; Sinha et al, 2020 ; Subbaiyan et al, 2020 ). A number of studies that can be found on the World Health Organization's International Clinical Trials Registry Platform also involve plant-based compounds, particularly flavonoids.…”