Dengue virus (DENV) serotype remains a global health concern, particularly within the tropical and subtropical regions, where outbreaks could lead to severe morbidity and mortality. Targeting the NS2B-NS3 protease complex is, therefore, an indispensable step for the virus to replicate and mature. Accordingly, it has emerged as a highly promising target in the discovery of agents for diseases caused by DENV. Thus, we herein report advanced computational techniques for drug-designing experiments toward NS2B-NS3 protease inhibitor screening by molecular docking simulations. We screened a diverse library of 645 ligand compounds taken from PubChem, comprising an array of phytochemicals and synthetically derived, which have shown some potential therapeutic use. Noting that molecular docking analysis and 200ns time frame molecular dynamic simulations facilitated the evaluations of binding affinities and intermolecular interactions between the ligands and the NS2B-NS3 protease. Out of the screening, four ligands that were the highest candidates for interacting with the target were identified. Of these, PubChem CID: 136448014, was the one ligand that had the highest binding affinity of -9.394 kcal/mol, suggesting that this compound is a strong potential inhibitor. This compound is showing promising effects, which could warrant further studies to evaluate its efficacy in inhibiting DENV viral properties. The findings indicate a strong impetus for the use of computational techniques in drug discovery for developing targeted antiviral therapies against DENV infections, thus enhancing our collective fight against this threat of public health. Experimental validation and subsequent optimization of this compound will be essential for its confirmation as a potential therapeutic candidate in the clinic.
Bharathi et al. (Thu,) studied this question.