The realm of host–pathogen interactions (HPIs) spans a diverse spectrum of biological occurrences. Within this domain, hosts are represented by both humans and plants, while pathogens encompass a variety of agents, such as viruses, fungi, and bacteria. These interactions serve as foundational elements in the fields of immunology, microbiology, pathology, and medicine. They hold a central role in unveiling the intricate workings of pathogen invasion, host defense mechanisms, and the formulation of strategies for disease prevention and treatment. Computational approaches have emerged as potent tools for studying HPIs, especially in the case of human–virus protein-protein interactions (Hu–Vir PPI), enabling researchers to systematically explore how viruses invade and manipulate host cellular processes. This chapter serves as a comprehensive guide to the computational methods employed for the analysis of Hu–Vir PPI, offering insight into their utility and application.