Unveiling <i>Allium sativum</i> Phytocompounds as New Antileptospiral Agents via a Structural‐Based Virtual Screening Approach

Abstract Leptospirosis, a disease of zoonotic origin, is transmitted to humans via the Leptospira bacteria, which infected rats and domestic animals carry. This disease is prevalent in certain regions of South India and North‐East India. As per the Leptospirosis Burden Epidemiology Group (WHO), there are approximately 873,000 reported cases and 48,600 deaths annually. Interestingly, we have identified specific targets that are vital to metabolic processes, lipid synthesis, the flagellar motor protein system, and bacterial chemotaxis. By developing new drugs that target these areas, we could significantly mitigate the risks associated with severe Leptospirosis. This study aims to create a new antileptospiral drug using data from the IMPPAT database. We performed virtual screening with Schrodinger, molecular dynamic simulation, and free energy investigation using GROMACS throughout 50 ns. The primary objective was to identify eight potential therapeutic targets in Leptospira for drug development. The screening process successfully identified promising drug candidates for the treatment of Leptospirosis, specifically IMPHY015116, IMPHY004388, IMPHY004619, IMPHY014919, IMPHY007598, and IMPHY001246. These phytochemical compounds exhibit higher binding energy than conventional drug molecules and show stability in dynamic environments. However, additional studies are required to validate their effect on disease progression and pathogenicity through in vitro studies.