Computational approaches for designing viral protease inhibitors

Viral proteases are critical enzymes that play essential roles in the replication of viruses such as Human Immunodeficiency, Hepatitis C, SARS-CoV-2, Zika, Dengue, West Nile, Yellow Fever, Japanese and Saint Louis Encephalitis, Tick-Born Encephalitis, Chikungunya, and others. Designing potent inhibitors against these proteases has been a major therapeutic strategy to control and treat these viral infections. Computational approaches, including structure-based drug design, ligand-based drug design, machine learning and artificial intelligence-based techniques, have significantly accelerated the discovery and optimization of viral protease inhibitors. This chapter provides an in-depth review of the computational methodologies employed in the development of inhibitors for these major viral targets, highlighting case studies for each virus, discussing strategies to overcome resistance, and exploring future directions in antiviral drug discovery.