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Novel nanobody effective against henipaviruses

Researchers have discovered a strategy to neutralise two highly lethal henipaviruses for which there is currently no approved vaccine or cure.

An Austrailian team led by Professor Daniel Watterson and Dr Ariel Isaacs at The University of Queensland (UQ) has identified the first ever nanobody to work against Nipah and Hendra, henipaviruses which have jumped from animals to people in Asia and Australia. Their research has been published in Nature Structural and Molecular Biology

“A nanobody is one-tenth the size of an antibody and being that small it can access hard-to-reach areas of a virus to block infection,” Dr Isaacs said. “Nanobodies are also easier to produce and more stable at higher temperatures than traditional antibodies, so we are very excited about the potential of our discovery to lead to new treatments.” Dr Ariel Isaacs is pictured with a model of DS90 nanobody in yellow bonded into a Nipah virus fusion protein.

The nanobody, called DS90, was among a series isolated by research partners at Universidad Austral de Chile from the immune cells of an alpaca called Pedro. Camelids, including alpacas, are the only land animals which produce nanobodies. DS90 was identified via a platform developed by Professor Alejandro Rojas-Fernandez which can isolate nanobodies against viruses of concern.

Tests at Professor Watterson’s laboratory at UQ’s School of Chemistry and Molecular Biosciences confirmed DS90 could bind successfully to proteins in Nipah and Hendra viruses and block their ability to enter cells.

“We could see exactly how the nanobody bound to the virus reaching right into deep pockets, whereas antibodies typically just bind to exposed surfaces of viruses,” Professor Watterson said. “This new information is a crucial step towards using a nanobody to combat Hendra and Nipah, which cause outbreaks in people and can often lead to fatal respiratory and neurological disease.”

The team also combined the DS90 nanobody with a developmental antibody therapy that is used as a last resort treatment for people infected with Hendra and Nipah, showing that the combination of DS90 with the m102.4 antibody prevents Nipah virus from mutating and evolving.

Other nanobodies have previously been approved for use as cancer treatments and this research shows that nanobodies can also be used to neutralise viruses. The next step will be to translate the findings into a therapeutic to be clinically ready in case of an outbreak of Hendra or Nipah.

The UQ research project was supported by the work of Professor Alejandro Rojas-Fernandez and Dr Guillermo Valenzuela Nieto at Universidad Austral de Chile, along with scientists at CSIRO’s Australian Centre for Disease Preparedness and the University of Science and Technology of China.

  • Isaacs A, Nieto GV, Zhang X, et al. A nanobody-based therapeutic targeting Nipah virus limits viral escape. Nat Struct Mol Biol. 2025 Jul 8. doi:10.1038/s41594-025-01598-2

 

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