Nipah virus (NiV) is a lethal bat-borne zoonotic virus that causes mild to acute respiratory distress and neurological manifestations in humans with a high mortality rate. NiV transmission to humans occurs via consumption of bat-contaminated fruit and date palm sap (DPS), or through direct contact with infected individuals and livestock. Since NiV outbreaks were first reported in pigs from Malaysia and Singapore, non-neutralizing antibodies against NiV attachment Glycoprotein (G) have also been detected in a few domestic mammals. NiV infection is initiated after NiV G binds to the host cell receptors Ephrin-B2 and Ephrin-B3. In this study, we assessed the degree of NiV host tropism in domestic and peridomestic mammals commonly found in Bangladesh that may be crucial in the transmission of NiV by serving as intermediate hosts. We carried out a protein-protein docking analysis of NiV G complexes (n = 52) with Ephrin-B2 and B3 of 13 domestic and peridomestic species using bioinformatics tools. Protein models were generated by homology modelling and the structures were validated for model quality. The different protein-protein complexes in this study were stable, and their binding affinity (ΔG) scores ranged between -8.0 to -19.1 kcal/mol. NiV Bangladesh (NiV-B) strain displayed stronger binding to Ephrin receptors, especially with Ephrin-B3 than the NiV Malaysia (NiV-M) strain, correlating with the observed higher pathogenicity of NiV-B strains. From the docking result, we found that Ephrin receptors of domestic rat (R. norvegicus) had a higher binding affinity for NiV G, suggesting greater susceptibility to NiV infections compared to other study species. Investigations for NiV exposure to domestic/peridomestic animals will help us knowing more the possible role of rats and other animals as intermediate hosts of NiV and would improve future NiV outbreak control and prevention in humans and domestic animals.
Nipah virus (NiV) is a zoonotic paramyxovirus belonging to the genus Henipavirus, which infects Pteropus bat species in Southeast and South Asia. Since its discovery in the late 1990s in Malaysia, NiV has caused outbreaks in humans in Singapore, Bangladesh, India and the Philippines. The spillover pathway for the most recent NiV outbreak in 2023 in Kerala, India, remains speculative. NiV causes serious disease in infected humans, with a mean case-fatality rate of 70%, and no approved treatment or vaccines exist. Humans have been infected directly from bats through shared food or through infected bridging hosts, including pigs and horses, although other spillover pathways may exist. Here, we review the pathways of NiV spillover and transmission, highlighting areas needing further research. We emphasize the importance of collaborative and multidisciplinary efforts both in the laboratory and in the field, and the implementation of a One Health strategy to prevent future epidemics.