An In Silico Study of Phytochemicals of Cissus quadrangularis as Resources for Docking With Main Protease of SARS COV-2 and Comparative Analysis

Abstract

Investigating structurally varied ethnopharmacological scaffolds is still essential for finding long-lasting inhibitors against SARS-CoV-2, despite a great deal of research on synthetic antivirals. Cissus quadrangularis is a well-known medicinal succulent that is highly prized for its rich therapeutic profile of secondary metabolites. However, its unique multi-constituent strategy against the essential viral replication enzyme, the main protease (M^pro), is still unknown. By performing a comparative structural screening of phytoconstituents from C. quadrangularis against the catalytically active dimeric form of SARS-CoV-2 M^pro via docking and simulation analyses, this study filled this knowledge gap. The M^pro dimer of COVID-19 was significantly inhibited by the top ranked phytochemicals of C. quadrangularis viz. luteolin (−7.7 Kcal/mol), quercetin (−7.3 Kcal/mol), kaempferol (−7.2 Kcal/mol), adrenosterone (−7.8 Kcal/mol), resveratrol (−7.0 Kcal/mol), piceatannol (−6.9 Kcal/mol), etc. which had the binding energies indicating their potential for additional in vitro research. These results elucidated the structural and thermodynamic framework behind C. quadrangularis's predicted target interaction, offering a clear computational rationale for prioritizing its specific flavonoid and stilbene components as candidates lead for mandatory future in vitro validation. The molecular docking of M^pro dimer of COVID-19 was visualized using PyMOL and Ligplot.