Nipah virus (NiV) is a zoonotic pathogen, first identified in Malaysia in 1998. It is a member of the Paramyxoviridae family, genus Henipavirus. NiV infections cause severe respiratory and neurological diseases in both humans and animals. Fruit bats of the Pteropodidae family are natural hosts of NiV.
Human-to-human transmission has been documented, with transmission through direct contact with infected bats, pigs, or people.
Incubation period is typically 4-14 days, with some cases reported up to 45 days.
Early Symptoms are Fever, Headache, Myalgia, Sore throat, Vomiting etc. Severe Symptoms include Acute respiratory distress, Encephalitis, Seizures , Altered mental status and Coma
NiV has a complex pathophysiology involving multiple organ systems. The virus can enter through respiratory routes or through consumption of contaminated food (e.g., date palm sap). Primary Replication Sites are epithelial cells in the respiratory tract or gastrointestinal tract. Virus spreads to regional lymph nodes and then to the bloodstream (viremia).
Nipah virus (NiV) encodes two key glycoproteins critical for its entry and pathogenesis: the fusion (F) glycoprotein and the attachment (G) glycoprotein. These glycoproteins play essential roles in viral attachment to host cells, fusion of the viral and cellular membranes, and subsequent entry of the viral genome into the host cell.
Attachment Glycoprotein (G) is a type II transmembrane protein. It mediates attachment of the virus to the host cell receptors. The primary receptors for NiV G glycoprotein are ephrin-B2 and ephrin-B3. Binding of the G glycoprotein to ephrin-B2/B3 receptors triggers conformational changes that activate the F glycoprotein, facilitating membrane fusion. The interaction between G glycoprotein and ephrin-B2/B3 is critical for the virus’s ability to infect endothelial and neuronal cells, leading to the characteristic vascular and neurological manifestations of NiV infection.
Fusion Glycoprotein (F) is a class I viral fusion protein, synthesized as a precursor (F0) that is cleaved into two subunits, F1 and F2, linked by a disulfide bond. The F glycoprotein facilitates the fusion of the viral envelope with the host cell membrane, allowing entry of the viral RNA into the host cell cytoplasm. After the G glycoprotein binds to the host cell receptor, the F glycoprotein undergoes a series of conformational changes, resulting in the insertion of the fusion peptide into the host cell membrane and subsequent fusion of the viral and cellular membranes. The F glycoprotein’s fusion activity is essential for viral entry and cell-to-cell spread, contributing to the formation of multinucleated giant cells (syncytia), a hallmark of NiV infection in tissue cultures.
The ability of NiV G and F glycoproteins to mediate entry into endothelial cells is a key factor in the virus’s capacity to cause vasculitis and widespread vascular damage. The affinity of NiV glycoproteins for ephrin-B2/B3 receptors, which are highly expressed in the central nervous system, underpins the virus’s neurotropism and resultant encephalitis. Glycosylation of the G and F glycoproteins may aid in evading host immune responses by masking critical epitopes from neutralizing antibodies.
Targeting the G and F glycoproteins with neutralizing monoclonal antibodies has shown promise in preclinical studies. These antibodies can block the interaction of the G glycoprotein with its receptors or inhibit the fusogenic activity of the F glycoprotein. Glycoproteins are key antigens in the development of NiV vaccines. Subunit vaccines incorporating the G and/or F glycoproteins have demonstrated protective efficacy in animal models.
NiV glycoproteins are critical determinants of the virus’s pathogenicity and host range. Understanding their structure, function, and interaction with host receptors provides valuable insights into the mechanisms of NiV infection and pathogenesis, and informs the development of targeted therapies and vaccines.
NiV targets endothelial cells, leading to widespread vasculitis. Infection spreads to small blood vessels in the brain, lung, kidney, and other organs, causing thrombosis and hemorrhage. Through infected endothelial cells, the virus disseminates to various organs.
NiV can cross the blood-brain barrier, leading to encephalitis. Brain involvement causes inflammation, necrosis, and vasculitis in the brain. Affected areas include the brainstem, thalamus, and cortex. Neurological manifestations include confusion, disorientation, drowsiness, and seizures.
Infection can cause severe respiratory symptoms, including acute respiratory distress syndrome (ARDS). NiV infects epithelial cells of the respiratory tract, causing necrosis and hemorrhage in lung tissues.
Diagnostic Methods include RT-PCR for detection of viral RNA from throat/nasal swabs, cerebrospinal fluid, urine, or blood, serological tests for detection of IgM and IgG antibodies, Virus Isolation from clinical samples in specialized labs and MRI/CT Scans to detect brain involvement and assess encephalitis.
Mainstay of treatment includes intensive supportive care, such as mechanical ventilation and management of seizures. Even though with limited evidence, ribavirin has been used in some cases. Experimental therapies involving monoclonal antibodies (e.g., m102.4) are under investigation.
Prevention and Control includes surveillance of animal populations, especially fruit bats and pigs, and quarantine and culling of infected animals.
Use of protective equipment by healthcare workers, Isolation of infected patients and Community awareness and education are also important.
Research is ongoing to develop effective vaccines for NiV.
Nipah fever is a severe, often fatal zoonotic infection with significant public health implications. Early detection, supportive care, and stringent preventive measures are crucial to managing outbreaks. Understanding the pathophysiology is essential for developing targeted therapies and improving patient outcomes.
MIT HOMEOPATHY requests scientific community to take up serious research for development of molecular imprints of nipah viral glycoproteins, to be used for prevention and treatment of nipah virus infection. These molecular imprints can act as artificial binding pockets for nipah glycoproteins, thereby preventing their pathological interactions with biological molecules. Molecular imprints of nipah glycoproteins will be 100% safe to use, as they will not contain molecular forms of the viral material.
REDEFINING HOMEOPATHY 
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