Nipah Virus is Scaring the World Again: Current Therapeutic Developments, Antivirals, Antibodies, and Vaccines

Abstract

Nipah virus (NiV) is a zoonotic paramyxovirus of the genus Henipavirus that periodically erupts in South and South-east Asia, causing lethal encephalitis and respiratory disease in humans with case fatality rates historically ranging between 40% and 100%. Originally identified during a large outbreak in Malaysia and Singapore between 1998 and 1999, NiV has since caused repeated outbreaks in Bangladesh and India, with fruit bats of the genus Pteropus serving as the primary natural reservoir. The absence of approved vaccines or specific antiviral therapeutics for human use renders NiV a continued and escalating global health threat; the pathogen appears on the World Health Organization's list of priority diseases requiring urgent research and development attention. This narrative review surveys the current landscape of therapeutic candidates targeting NiV, encompassing nucleoside analogue antivirals, monoclonal antibodies, and vaccine platforms at various stages of preclinical and early clinical development. Remdesivir (GS-5734), originally developed against Ebola virus, has demonstrated compelling efficacy in African green monkeys exposed to NiV, whilst favipiravir (T-705) has shown protective activity in hamster models, together representing the most advanced antiviral candidates. The human monoclonal antibody m102.4 has progressed furthest among immunotherapeutics, affording postexposure protection in nonhuman primates and receiving compassionate-use administration in Hendra virus-exposed patients in Australia. Vaccine candidates based on soluble subunit proteins, chimpanzee adenovirus-vectored constructs (ChAdOx1), and recombinant vesicular stomatitis virus (rVSV) vectors have each demonstrated complete protection in nonhuman primate models, with several entering or approaching Phase I human trials. Despite this progress, the absence of endemic infrastructure for clinical trials, limited commercial incentive, and the sporadic nature of outbreaks collectively impede therapeutic advancement. Coalition for Epidemic Preparedness Innovations (CEPI) funding and WHO coordination have been instrumental in accelerating the pipeline. This review critically evaluates the evidence base for each therapeutic class, identifies gaps in knowledge, and proposes priorities for the next phase of research.