ABSTRACT
Coronavirus disease 2019 (COVID-19) caused appalling conditions over the globe, which is currently faced by the entire human population. One of the primary reasons behind the uncontrollable situation is the lack of specific therapeutics. In such conditions, drug repurposing of available drugs (viz. Chloroquine, Lopinavir, etc.) has been proposed, but various clinical and preclinical investigations indicated the toxicity and adverse side effects of these drugs. This study explores the inhibition potency of phytochemicals from Tinospora cordifolia (Giloy) against SARS CoV-2 drugable targets (spike glycoprotein and Mpro proteins) using molecular docking and MD simulation studies. ADMET, virtual screening, MD simulation, postsimulation analysis (RMSD, RMSF, Rg, SASA, PCA, FES) and MM-PBSA calculations were carried out to predict the inhibition efficacy of the phytochemicals against SARS CoV-2 targets. Tinospora compounds showed better binding affinity than the corresponding reference. Their binding affinity ranges from -9.63 to -5.68 kcal/mole with spike protein and -10.27 to -7.25 kcal/mole with main protease. Further 100 ns exhaustive simulation studies and MM-PBSA calculations supported favorable and stable binding of them. This work identifies Nine Tinospora compounds as potential inhibitors. Among those, 7-desacetoxy-6,7-dehydrogedunin was found to inhibit both spike (7NEG) and Mpro (7MGS and 6LU7) proteins, and Columbin was found to inhibit selected spike targets (7NEG and 7NX7). In all the analyses, these compounds performed well and confirms the stable binding. Hence the identified compounds, advocated as potential inhibitors can be taken for further in vitro and in vivo experimental validation to determine their anti-SARS-CoV-2 potential.Communicated by Ramaswamy H. Sarma.