Pharmacological Research - Modern Chinese Medicine (Dec 2023)
In silico study unravels binding potential of madecassic acid against non-structural proteins of SARS-CoV-2
Abstract
Backgrounds: COVID-19 is the ongoing global health emergency caused by SARS-CoV-2. Virions have multiple spike-glycoproteins on their surface to corrupt the host cells. Viral genome encodes for non-structural proteins 1–16 (NSP1–16) that orchestrate viral replication and immune evasion. Therefore, targeting NSPs with potential therapeutic compounds could help to combat COVID-19. Centella asiatica and C. erecta are the two herbaceous plants, indigenous to China. These nutritious herbs are enriched with a bioactive compound referred to as madecassic acid (MDCA). MDCA has been employed as traditional folk medicine in China for hundreds of years. It has several health benefits and treats dermatitis, neurological disorders, inflammatory diseases, and metabolic ailments. It has also been detected to exert antiviral activities against hepatitis B virus and herpes simplex virus. Nevertheless, its efficacy as anti-SARS-CoV-2 agent has not been investigated. Hence, the present study aimed to explore the inhibitory potential of MDCA against viral NSPs. Methods: In silico study was conducted to explore the binding affinities of MDCA against the NSPs of SARS-CoV-2 that are critical for viral replication and pathogenesis. For the purpose, MDCA and various NSPs were retrieved from PubChem and Protein Data Bank respectively. The compound and the protein molecules were processed and allowed to dock employing AutoDock Vina. Subsequently, the intermolecular interactions between proteins and MDCA were visualized using ChimeraX and Discovery Studio Visualizer. Results: Results of the study revealed that MDCA can interact with ligand-binding pockets of NSPs with optimum free-energies. Moreover, MDCA blocks several amino acid residues of NSPs through various hydrogen bonds and other non-covalent interactions. These interactions have the efficiency to impede catalytic activities of NSPs, leading to reduced infection and pathogenicity. Conclusion: Intermolecular binding with MDCA and NSPs might trigger an allosteric modification in functional moieties of these proteins. Such modifications could subvert the catalytic functions of targeted proteins. Therefore, MDCA can be considered in future studies and clinical trials as a potential cost-effective, anti-SARS-CoV-2 compound with multi-target efficacy. However the present results require further validation using in vitro and in vivo settings.
