Molecular Docking Analysis of the Phytochemicals from Tinospora Cordifolia as Potential Inhibitor Against Multi Targeted SARS-CoV-2 & Cytokine Storm

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2, a novel coronavirus, is a member of the Coronoviridae family that has spread worldwide. Developing efficacious therapeutics for the treatment of SARS-CoV-2 is of high priority. Therefore, in this study, the chemical constituents obtained from Tinospora cordifolia are investigated for their in-silico interaction with protein targets crucial for SARSCoV-2 infection and cytokine storm. The five important targets chosen for SARSCoV-2 were the main protease (Mpro), Spike receptor binding domain (Spike-RBD), RNA-dependent RNA polymerase (RdRp or Nsp12), nonstructural protein 15 (Nsp15) of SARS-CoV-2 and the host angiotensin converting enzyme-2 (ACE-2) spike-RBD binding domain and cytokine receptors TNF-[Formula: see text] (Tumor Necrosis Factor-[Formula: see text]) and IL-6 (Interleukine-6). This was accomplished using Maestro 12.4 (Schrodinger Suite) to obtain docking scores. Also, the absorption, distribution, metabolism, elimination, and toxicity parameters (ADMET) were determined using Maestro QikProp modules. The results of computational study revealed that four constituents Cordifolioside-A, Palmatoside-E, Tinocordioside and Tinosporaside significantly antagonize the five targets of SARS-CoV-2 by binding in the binding pocket with docking score ranging from −9.664 to −6.488 kcal/mol and shows drug-like property and also effectively inhibit cytokine storm by antagonizing the TNF-[Formula: see text] and IL-6 receptors. Promising drug-like properties, excellent docking scores, and binding pose against each target makes the screened compounds as possible lead candidate which can be further evaluated in future studies to assess their in vitro and in vivo efficacy against SARS-CoV-2. The structure of these compounds can be used further for optimization and design of drugs against COVID-19.