V.A. JADHAV*,**,#, SUJATA INGLE*, R. AHMED*
*School of Life Sciences, ”Swami Ramanand Teerth Marathwada” University, Nanded, 431606 (MS), India, e-mail: firstname.lastname@example.org
**Department of Biophysics, ”Digambarrao Bindu” College, Bhokar, Nanded District, 431801 (MS), India
The pandemic situation caused by SARS-CoV-2 is responsible for the coronavirus infectious disease-19 (COVID-19) around the globe. Recently reported highly modulated enzyme main protease complex (Mpro) was responsible for coronavirus replication and transcription. This significant function of Mproattracts as potential candidates for drug targets. Naturally, Tinospora cordifolia was found effective against cancer, HIV, viral infections and diabetes. One of the most effective alkaloid palmatine present in T. cordifolia. In present study, we have investigated potential activity of palmatine against Mpro. Physico-chemical properties were analyzed by the ProtParam tool; structure prediction and homology modeling were carried out by the SWISS-MODEL server. Significant superimposition structure, equal global model quality estimation (GMQE) and quaternary structure quality estimate (QSQE) values were found for eight highly similar templates. Ramachandran plot (97.67 % favored), local quality estimate ratio (>0.6), and higher qualitative model energy analysis (QMEAN) score (y-axis) assessments were performed for structural validation of Mpro. Further, the SwissDock server was used to perform docking between validated targets Mpro with ligand palmatine. The significant ΔG value –8.281919 kcal·mol–1 indicates reliable docking interaction. Comparative docking among palmatine, gingerol and berberine suggests palmatine interacts efficiently with Mpro. Thus, an attempt was made to find a potent inhibitor, as there is no promising and specific antiviral drug or vaccine available for the prevention and treatment of COVID-19 infections. However, in vitro studies are required to validate our predictions. Whereas, toxicological studies reported against palmatine for acute effect (135 mg/kg body weight) on mouse model LD50.
Key words: Palmatine, SARS-CoV-2, main protease complex, homology modelling, docking.