Exploring the Inhibitory Potential of Bioactive Compounds from Bael Leaves against Dengue Ns3 Helicase—A Computational Investigation

ABSTRACT Dengue, rapidly evolving arboviral disease, has a profound impact on human health worldwide. The increase in dengue cases reinforces the urgent need for developing effective therapies. Despite recent advancements in dengue research, the presence of four antigenically distinct serotypes, antibody‐dependent enhancement, and the lack of preclinical animal models slow down drug development. In this context, bioactive compound‐abundant medicinal plants offer a promising alternative owing to their immense therapeutic potential. Their traditional uses against infectious diseases provide a sound basis for their exploration in the current anti‐dengue drug discovery. However, in‐depth scientific validation is necessary to ensure their safety and efficiency. The present study aimed to evaluate the anti‐dengue potential of phytochemicals from Aegle marmelos leaf extract using in silico approaches. The virtual screening results identified four top hit compounds: Kuwanon Z, Bebeerine, Tiliacorine, and Ganosporelactone A. These hit candidates were further investigated for pharmacokinetic and toxicokinetic analysis. Molecular dynamics simulation studies were conducted to understand the dynamic behavior and structural constancy of the dengue virus helicase domain upon interaction with the top‐hit compounds. Among the investigated hits, Kuwanon Z demonstrated enhanced binding affinity and structural stability with the helicase domain, highlighting its potential as a promising lead compound for dengue.