eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2025-12-30 18 4 3114 3137 10.13005/bpj/3322 69613 article Fabian Mok Ping Xiang 1 Vasudeva Rao Avupati 2 School of Postgraduate Studies, IMU University (Formerly known as International Medical University), Kuala Lumpur, Malaysia Department of Pharmaceutical Chemistry, School of Pharmacy, IMU University (Formerly known as International Medical University), Kuala Lumpur, Malaysia Centre of Excellence for Bioactive Molecules & Drug Delivery (BMDD), Institute for Research, Development & Innovation (IRDI), IMU University (Formerly known as International Medical University), Kuala Lumpur, Malaysia The increasing frequency of global travel and migration has intensified the spread of viral infections, including COVID-19 (SARS-CoV-2), Hepatitis C (Hepatitis C virus, HCV), acquired immunodeficiency syndrome (Human Immunodeficiency Virus, HIV), Dengue fever (Dengue virus, DENV), and Zika fever (Zika virus, ZIKV). These global health challenges underscore the urgent need for effective antiviral therapeutics. Viral protease enzymes play a vital role in the viral replication cycle, making them promising molecular targets for therapeutic intervention. In this study, structure-based pharmacophore modeling (SBPM) and molecular docking approaches were employed to identify potential protease inhibitors against multiple viral proteases. Pharmacophore models were generated for five viral targets obtained from the RCSB Protein Data Bank, followed by virtual screening of compound libraries from the ZINC and Molport databases. Top-ranked virtual hits were subsequently docked using iGEMDOCK to evaluate binding affinities and molecular interaction profiles, while physicochemical and pharmacokinetic properties were assessed using the SWISSADME web tool. The findings revealed several promising virtual hits exhibiting strong and stable binding interactions at the protease active sites, alongside favorable drug-likeness profiles. These results provide a valuable foundation for future in vitro validation, hit-to-lead optimization, and the potential development of novel antiviral agents targeting multiple viral proteases. https://biomedpharmajournal.org/vol18no4/identification-of-inhibitors-of-viral-proteases-by-virtual-screening-a-structure-based-pharmacophore-modelling-sbpm-and-molecular-docking-studies/ Dengue virus (DENV) Drug discovery Hepatitis C virus (HCV) Human Immunodeficiency Virus (HIV) Molecular docking SARS-CoV-2 Structure-based pharmacophore modeling (SBPM) Viral protease inhibitors Virtual screening Zika virus (ZIKV)