Assessing the pandemic potential of Nipah virus: From molecular pathogenesis to ecological spillover risks

Nipah virus, a highly lethal zoonotic paramyxovirus with a case‑fatality rate of 40-75%, poses a formidable threat to global health security. This review synthesizes its evolving epidemiology, contrasting the Malaysian and Bangladesh‑India strains, and dissects molecular pathogenesis focusing on G/F glycoprotein recognition of ephrin receptors and the multi‑layered immune evasion mediated by P gene products. Phylogenetic analyses reveal 8-10% nucleotide divergence between lineages, with positive selection in the G protein that may compromise vaccine cross‑protection. Ecological risk amplifiers-deforestation and climate‑driven habitat loss-reshape spillover dynamics through spatial expansion of bat foraging, prolonged risk windows, and pathway diversification. Deforestation exceeding 5% per decade correlates with a 2-3‑fold increase in spillover events in Bangladesh. A dynamic risk‑assessment framework is proposed that views pandemic potential as the convergence of viral evolution, ecological amplification, and geographic expansion-from South Asia to Pteropus‑bearing regions worldwide, including unrecognized risks in China. Current medical countermeasures (mRNA vaccines, m102.4 antibody, remdesivir) and deployment challenges (genetic diversity, biosafety level 4 constraints, regulatory dependence on the "Animal Rule") are evaluated. The conclusion calls for a "One Health"‑informed global defense system anchored on four pillars: intelligent forecasting that integrates ecological data; a broadly protective countermeasure repository; democratized rapid diagnostics; and translational bridges linking molecular insights to actionable interventions. Strengthening global collaboration is imperative to prevent Nipah virus from escalating into a pandemic.