Exploring the Potential of Siddha Formulation MilagaiKudineer-Derived Phytotherapeutics Against SARS-CoV-2: An In-Silico Investigation for Antiviral Intervention

Author(s): Baskar Rajamanickam, Ramesh Balasubramanian, Manekshah Yovas Rajammal, Bharathkumar Govindaraju, Selvapriya Sikkal Selvaraaju, Hemadevi Thangarasu, Kanakavalli Kadarkarai

The search for effective therapeutics against COVID-19 remains imperative, and natural compounds have emerged as promising candidates. Our study explores the potential of bioactive phytochemicals from the traditional Siddha formulation MilagaiKudineer as inhibitors against key target proteins of the SARS-CoV-2 virus. Through in-silico docking analyses, the interactions of phytochemicals from Cuminum cyminum, Curcuma longa, and Capsicum annuum with the receptor-binding domain of the SARS-CoV-2 spike glycoprotein (PDB ID: 6VSB), the SARS-CoV2 RNA-dependent RNA polymerase (PDB ID: 6NUR), and the main protease, 3CL pro (PDB ID: 6LU7) were examined. Notable compounds such as Curcumin, Quercetin, Capsaicin, and Ascorbic acid demonstrated significant binding affinities towards these viral targets, suggesting mechanisms by which these phytochemicals may disrupt viral entry and replication. Our findings also highlight the potential of compounds like Carvacrol, Cuminaldehyde, Linalool, and Dihydrocapsaicin in mediating antiviral effects by interfacing with key amino acid residues of the spike glycoprotein. These interactions are indicative of their capacity to hinder the virus-host cellbinding process. Moreover, the interaction of select phytochemicals with the SARS-CoV2 RNA-dependent RNA polymerase and the 3CLpro enzyme suggests a possible inhibitory effect on viral replication. Given the promising interactions observed, these phytochemicals warrant further investigation through in vitro and in vivo studies to validate their antiviral efficacy against COVID-19. This research underscores the importance of exploring traditional medicinal formulations for potential therapeutic agents in the fight against emerging infectious diseases.