Miniature llama antibodies could help fight SARS-CoV-2 variants

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Amid the growing threat of a potentially more dangerous new SARS-CoV-2 variant, scientists are stepping up the search for more potent treatments. A new study now demonstrates the therapeutic potential of an unusual class of immune proteins: miniature llamas-derived antibodies called nanobodies.

Rockefeller scientists Michael P. Rout and Brian T. Chait and their colleagues at the Seattle Children’s Research Institute selected a repertoire of more than a hundred nanobodies based on their potency and ability to target different parts of the protein of spike of SARS-CoV-2.

Produced by immune llamas, the nanobodies have been shown to neutralize the original coronavirus and several of its variants, including Delta, with high efficacy in laboratory tests. Studies to assess their potency against the new Omicron variant are ongoing.

The researchers hope that a combination of nanobodies could be developed into an effective COVID treatment against current and future variants.

“Based on how our nanobodies bind to the virus, we hope many will remain effective, perhaps even against Omicron,” Rout says. “We should have those results soon.”

The results are published in the journal eLife.

The path to a new treatment

A human antibody is a chunky formation of two protein chains. But llamas, camels and other species of the camelid family make antibodies made up of a single protein.

To obtain the nanobodies, the researchers took blood samples from llamas that had received small doses of vaccine-like coronavirus proteins. They then sequenced the DNA corresponding to various nanobodies produced by the immune system of llamas and expressed these genes in bacteria to produce large quantities of nanobodies for laboratory analysis. Nanobodies that exhibited the desired properties were then selected and tested further to identify those most capable of neutralizing the virus.

The small size of the nanobodies allows them to access hard-to-reach points on the SARS-CoV-2 virus that larger antibodies may not be able to access. It also allows researchers to combine nanobodies that can hit different parts of the virus, minimizing its chances of escaping.

“One of the most amazing things we’ve seen with nanobodies is that they show extraordinary synergy,” Chait says. “The combined effect is far greater than the sum of its parts.”

The researchers’ next plan is to test the safety and effectiveness of the nanobodies in animal studies.

In addition to being small and nimble, nanobodies are also inexpensive to mass-produce in yeast or bacteria. In addition, they are remarkably stable. The ability of these molecules to withstand high temperatures and long storage times means that they could be developed into an accessible medicine in various settings around the world.

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Material provided by Rockefeller University. Note: Content may be edited for style and length.

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