Abstract: Plant-based antiviral proteins (PAVPs) are key elements of the innate immune system in plants, offering protection against a wide array of viral pathogens. These proteins employ biochemical and molecular mechanisms to suppress viral replication, degrade viral RNA, and activate host defense pathways, making them valuable for applications in both agriculture and medicine. This review provides a comprehensive analysis of the antiviral mechanisms exhibited by PAVPs, summarizes the experimental and computational methodologies used to study them, and explores their potential applications in plant virology and biomedical research. This review systematically examines the landscape of PAVPs, integrating experimental and computational findings from the past 15 years. Evidence was collected from PubMed, Scopus, Web of Science, and Google Scholar (2010–2025) and filtered to include only proteinaceous agents. PAVPs exhibit diverse antiviral actions, including ribosome inactivation, RNase and protease activity, and interference with viral entry and replication. Experimental approaches such as TCID₂⁽ assays, protein interaction studies, and gene expression profiling have advanced our understanding of their function. Computational techniques—including molecular docking, dynamics simulations, and structure-function prediction—have further accelerated their characterization. These insights have led to practical applications ranging from virus-resistant crops to novel antiviral therapeutics and vaccines. This review provides a comprehensive synthesis across three dimensions: (i) mechanistic diversity of direct and host-mediated antiviral pathways, (ii) integration of laboratory and In silico methodologies, and (iii) translational potential in agriculture, medicine, veterinary science, and pandemic preparedness. Unlike prior reviews focused narrowly on single protein classes, this multi-angle approach highlights broader opportunities and limitations. Plantderived antiviral proteins represent a promising avenue for developing sustainable and effective antiviral strategies. Their mechanistic diversity, combined with modern research tools, holds significant potential for breakthroughs in plant protection, therapeutic development, and global health initiatives.
Maddi et al. (Mon,) studied this question.