Cordifolioside: potent inhibitor against M(pro) of SARS-CoV-2 and immunomodulatory through human TGF-β and TNF-α

Manne, Munikumar; Goudar, Giridhar; Varikasuvu, Seshadri Reddy; Khetagoudar, Mahadev C.; Kanipakam, Hema; Natarajan, Pradeep; Ummiti, Muni Divya; Yenagi, Vijay Aravind; Chinthakindi, Sridhar; Dharani, Prakash; Thota, Durga Sai Sri; Patil, Sameer; Patil, Vijaylaxmi

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.