Institute of Advanced Virology (IAV), an autonomous institution under Kerala Government's Science and Technology Department, is on the verge of a breakthrough in Nipah virus research. Studies to develop monoclonal antibodies, and also viral entry inhibitors or antivirals to fight the disease are at an advanced stage.

At present, there are no approved antiviral drugs for Nipah and supportive care is the only option for human infections. Moreover, monoclonal antibodies are imported from Australia in cases of emergency. A group of researchers at IAV, under senior principal scientist Dr Mohanan Valiya Veettil, is trying to develop monoclonal antibodies against Nipah. If successful, it will revolutionise the treatment of Nipah.

Monoclonal antibodies work to neutralise the virus. Like the coronavirus, the Nipah virus (NiV), too, has spikes around it. These spikes protrude through the membrane of the virus. These spikes that function like pointed nails are called glycoproteins (G-proteins). It is these G-proteins that help the virus to attach and infect the host cell.

"Thus, developing monoclonal antibodies that bind to the G protein can block the viral attachment and subsequent infection. For developing such monoclonal antibodies against NiV G-protein we use small animal models and hybridoma technology," said Dr Mohanan.

Monoclonal antibodies, if administered in time, can reduce the viral load in the patient's body. Monoclonal treatment is crucial because, for the body's immune system to muscle up, it takes time, sometimes even two weeks. By then, the virus would have swept through the body.

The virus first attacks the epithelial cells lining the respiratory system, where it multiplies, and then the viral swarm is released into the bloodstream, which functions as the highway that reaches the viral load swiftly to other organs, including the nervous system. This would result in encephalitis or inflammation of the brain.

This is why Nipah has a doomsday-like fatality rate upwards of 80 per cent. "As the viral load would increase in the patient's body rapidly upon infection, early administration of monoclonal antibodies is crucial in the treatment of this disease," Dr Mohanan said.

To check the efficacy of monoclonal antibodies, and also entry inhibitors or antivirals, the IAV team has developed what is called the Nipah virus-like particles (VLPs).

The Nipah virus genome encodes six major proteins: glycoprotein (G) or the spikes, fusion protein (F), matrix (M), nucleocapsid (N), long polymerase (L) and phosphoprotein (P). For the creation of VLPs, the IAV study did away with three proteins critical for replication -- N, P, and L -- and used only M (necessary for viral particle formation and budding), and the other two (G and F) vital for attachment and entry into the susceptible host cell.

The virus-like particle (VLP) thus formed mimicked the NiV in looks, behaviour and infectivity except for its reproductive capabilities. It is like the original virus being subjected to a kind of viral vasectomisation.

The lack of viral genetic material makes the particle non-infectious and safe to be handled in a BSL2 (biosafety level 2) laboratory, where moderate-risk biological agents are handled. The real NiV, being highly infective, can be handled only in BSL4 labs, designed for the highest level of biological safety.

The IAV team has used this NiV VLPs to study the entry of the virus and trace its path to the receptor cell of the host. "However, further experimental proofs are required," Dr Mohanan said.

Once the point of entry of Nipah virus is known, the team will experiment with the various antiviral drugs that could stop the virus from attaching to the receptor cell of the host.

If monoclonal antibodies smothers the spike proteins before it strikes the host, the inhibitors guard the receptor cells of the host from the attack of the NiV spikes.

The IAV team is confident in their current approach towards the development of an antiviral drug against Nipah virus.