Structural biology of Nipah virus G and F glycoproteins: Insights into therapeutic and vaccine development.

Abstract

Nipah virus (NiV), a highly pathogenic zoonotic paramyxovirus, poses a significant public health threat due to its high mortality rate and potential for human-to-human transmission. The attachment (G) and fusion (F) glycoproteins play pivotal roles in viral entry and host-cell fusion, making them prime targets for therapeutic and vaccine development. Recent advances in structural biology have provided high-resolution insights into the molecular architecture and functional dynamics of these glycoproteins, revealing key epitopes and domains essential for neutralizing antibody responses. The G glycoprotein's head domain and the prefusion F ectodomain have emerged as focal points for vaccine design, with multivalent display strategies showing promise in enhancing immunogenicity and breadth of protection. Structural studies have also informed the development of monoclonal antibodies like m102.4, offering potential post-exposure therapies. Additionally, insights from cryo-electron microscopy and X-ray crystallography have facilitated the design of structure-based inhibitors and next-generation vaccines, including nanoparticle and multi-epitope formulations. This review highlights recent structural findings on the NiV G and F glycoproteins, their implications for therapeutic strategies, and the challenges in developing effective and targeted interventions. A deeper understanding of these glycoproteins will be crucial for advancing NiV-specific therapeutics and vaccines, ultimately enhancing global preparedness against future outbreaks.