Structural insights into the Nipah virus life cycle: A framework for targeted therapeutic development

Nipah virus (NiV) is a highly lethal paramyxovirus designated by the World Health Organization as a priority pathogen. Despite its substantial pandemic potential, no approved vaccines or specific antiviral therapeutics are currently available. Existing neutralizing antibody-based therapies are constrained by limited breadth, vulnerability to viral escape, and suboptimal penetration into the central nervous system, underscoring the urgent need for next-generation interventions. This review details how high-resolution structural biology, by resolving the atomic architectures of key viral proteins—including the entry-mediating attachment glycoprotein (G) and fusion glycoprotein (F), the replication-executing large protein (L)–phosphoprotein (P) polymerase complex, and the assembly-driving matrix (M) protein—has mapped a comprehensive “druggable interface landscape” across the entire viral life cycle. These atomic blueprints are directly enabling rational design: from epitope-targeted multi-platform vaccines and antibody cocktails, to small-molecule inhibitors targeting polymerase allosteric pockets or essential protein–protein interactions, and forward-looking strategies for broad-spectrum agents and universal vaccine design. In summary, this work demonstrates that structural biology has transcended its traditional descriptive role to become the central engine driving a paradigm shift in antiviral development—from passive screening to active, precision design—thereby providing both a fundamental strategy and a translatable toolkit for confronting NiV and future emerging viral threats.