Countering Nipah Virus: A Review of Pathogenesis, Countermeasure Design, and Biosecurity Challenges

Nipah virus (NiV) is a zoonotic pathogen classified by the World Health Organization as a priority pathogen with epidemic potential.Driven by distinct viral lineages in Malaysia and Bangladesh, this pathogen can induce severe respiratory illness and lethal encephalitis, with human mortality rates ranging from ~40% to ~75% across outbreak zones, depending on the strain.This review paper focuses on the zoonotic origins and molecular mechanisms underlying NiV infection while highlighting both current medical countermeasures and emerging translational avenues to counter NiV's capacity for host immune evasion.By mapping out how these novel therapeutic strategies target the host-pathogen interface, we aim to inspire future countermeasure development and improve clinical outcomes for this biosecurity-relevant disease. Overview of Nipah VirusNipah virus (NiV) is an extremely pathogenic, zoonotic, single stranded RNA virus.Zoonotic viruses are viruses commonly transmitted to humans through animals.The pathogen exists in an animal reservoir where it can stay without dying out, eventually spreading to humans through infected animals or contaminated materials like food or fluids.Nipah virus is part of the family Paramyxoviridae, which is a family of enveloped, non-segmented, negative sense single stranded RNA viruses (Madhukalya et al., 2025).Members of the family will usually infect many mammals and birds, causing damage to the respiratory and nervous system.Viruses of the Paramyxoviridae family can range from common viruses like the measles virus and mumps virus all the way to lethal viruses such as Nipah virus (Madhukalya et al., 2025).Within that family, Nipah virus belongs to genus Henipavirus, a smaller group within the family that shares more commonalities.Members of genus Henipavirus tend to infect several different mammal species, are highly pathogenic, and can harbor a large number of hosts (Madhukalya et al., 2025).The most common hosts for viruses in this genus are fruit bats of genus Pteropus (Madhukalya et al., 2025).Hendra virus, a member of genus Henipavirus, is the closest relative to Nipah virus, and shares many commonalities, such as the same host and similar tissue tropism (Madhukalya et al., 2025).These similarities have led to attempts to utilize studies on Hendra in regards to finding antivirals and treatments for Nipah virus.Nipah virus contains a single stranded RNA genome, meaning genetic material is stored in RNA rather than DNA (Pellett et al., 2014).Single stranded means that the virus consists of only one RNA strand as opposed to the complementary strands of DNA (Pellett et al., 2014).However, this single strand means that Nipah, along with other RNA viruses, can mutate very fast, as RNA replication tends to be less accurate than DNA replication, allowing for more mutations to survive the replication process and pass their traits down (Madhukalya et al., 2025).In addition to being single stranded, Nipah virus is also negative-sense.This means that the virus cannot be used immediately to make proteins with the cell's organelles (Madhukalya et al., 2025).The RNA genetic sequence is already complementary to typical mRNA that can be translated into protein, so the virus must make a positive sense strand of RNA before protein production can begin (Pellett et al., 2014).This is done with RNA-dependent RNA polymerase