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.