Cordifolioside: potent inhibitor against Mpro of SARS-CoV-2 and immunomodulatory through human TGF-β and TNF-α

Abstract

Therapeutic options for SARS-CoV-2 are limited merely to the symptoms or repurposed drugs and non-specific interventions to promote the human immune system. In the present study, chromatographic and in silico approaches were implemented to identify bioactive compounds which might play pivotal role as inhibitor for SARS-CoV-2 and human immunomodulator (TGF-β and TNF-α). Tinospora cordifolia (Willd.) Miers was evaluated for phenolic composition and explored for bioactive compounds by high-performance thin layer chromatography (HPTLC). Furthermore, the bioactive compounds such as cordifolioside, berberine, and magnoflorine were appraised as human immunomodulatory and potent inhibitor against Main Protease (M pro ) of SARS-CoV-2 through multiple docking strategies. Cordifolioside formed six stable H-bonds with His41, Ser144, Cys145, His163, His164, and Glu166 of M pro of SARS-CoV-2, which displayed a significant role in the viral replication/transcription during infection acting towards the common conserved binding cleft among all strains of coronavirus. Overall, the study emphasized that the proposed cordifolioside might use for future investigations, which hold as a promising scaffold for developing anti-COVID-19 drug and reduce human cytokine storm.

Assessment of Antioxidant, Immunomodulatory Activity of Oxidised Epigallocatechin-3-Gallate (Green Tea Polyphenol) and Its Action on the Main Protease of SARS-CoV-2—An In Vitro and In Silico Approach

“…Other docking settings were left at their default parameters. For the structures, a PDBQT file was generated, which was then submitted to the molecular docking approach [ 29 ]. When the compounds interacted with macromolecules under rigid circumstances, they were in a flexible condition.…”

“…The AutoDock Vina scoring technique was used to determine negative Gibbs free energy (∆G) scores (kcal/mol) to estimate compound binding affinities. The distances between docked compounds and their interaction radii of 6 were calculated using Discovery Studio Biovia v2020 to determine the sizes of binding sites and the hydrogen bond and hydrophobic interactions they form [ 26 , 27 , 28 , 29 ]. For each compound’s interactions with the protein, binding poses were evaluated, and their most energetically favourable conformations were chosen [ 34 ].…”

In silicoinvestigation of the role of vitamins in cancer therapy through inhibition of MCM7 oncoprotein

“…The identification of active site (AS) and generation of receptor grid coordinates for MCM7 was performed using the BIOVIA Discovery Studio Visualizer v21.1.0.20298 (DSV). 33 …”

“…The molecular docking for each ligand was performed with the help of the Lamarckian Genetic Algorithm (LGA) in AutoDock Vina v1.2 (ref. 32 and 33 ) with 10 000 energy evaluations for twenty runs. Further, the protein–ligands complex's binding interactions were analyzed using BIOVIA DSV.…”

The Efficacy of Traditional Medicinal Plants in Modulating the Main Protease of SARS‐CoV‐2 and Cytokine Storm

“…[55] Besides, magnoflorine also displayed anti-cytokine storm potential. [81] Based on the above finding, it is pertinent to suggest T. cordifolia with immunomodulatory activities as a likely candidate to prevent oxidative damage and increase immune homeostasis response in Covid-19 patients. [82] The phytochemicals from T. cordifolia which exhibited drug-like effect is considered safe for human consumption.…”