IN SILICO INVESTIGATION OF INDIAN MEDICINAL HERBS FOR INFLUENZA MANAGEMENT: A FOCUS ON OCIMUM SANCTUM, WITHANIA SOMNIFERA, AND H1N1 NEURAMINIDASE TARGETING

Abstract

Influenza, classified within the Orthomyxoviridae family cause significant illness and death worldwide.The H1N1 subtype of influenza, causative of 2009 swine flu pandemic, triggered respiratorty tract infections in multiple species, including human, birds and swine is highly adaptable virus. It has a segmented genome , consisting of eight RNA segments. It undergoes rapid evolution through gradual accumulation of minor genetic changes in viral RNA (antigenic drift) and major genomic rearrangement through ressortment of RNA segments (antigenic shift ), which leads to emergence of new strain enabling the H1N1 to dodge immune response from the host and reduce impact of antiviral drugs. There are two critical surface protein hemaglutinin (HA) which mediates entry by recognizing sialic acid receptors present on host cells and neuraminidase(NA) ,which cleaves sialic acid residues to release the viral progeny .Currently NA targeting medications such as Oseltamivir(marketed as Tamiflu) and Zanmivir serve as effective .But due to its low efficacy in resistant H1N1 strains, has created an urgent need for novel antiviral compound with improved efficacy and resistance profile. This study aims to identify potential drug candidate derived from Withania somnifera and Ocimum sanctum ,targeting Neuraminidase using in silico approach called molecular docking. According to the docking studies, among all tested compounds, Withaferin A (Pubchem ID : 265237) demonstrated the most favorable overall pharmacological profile. Compared to Oseltamivir (Pubchem ID : 65028) with binding affinity -6.5 kcal/mol with NA and other phytocompounds, Withaferin A reflected the most negative binding affinity i.e. −9.2 kcal/mol, indicating a highly stable interaction with the NA. In ADMET profiling Withaferin A exhibited no Lipinski rule violations, high gastrointestinal (GI) absorption, acceptable bioavailability (0.55), and minimal CYP enzyme inhibition. Moreover, it is non mutagenic (Ames negative) and non-hepatotoxic, which are critical safety parameters. Being a phytochemical further adds to its drug-likeness potential. In contrast, Oseltamivir which is a synthetic drug and other phytocompounds either showed lower binding energy, Lipinski violations, poor GI absorption, or undesirable toxicity profiles. Thus, Withaferin A emerges as the most promising lead compound for further development.