Small antibodies offer broad protection against SARS coronaviruses

Small antibodies offer broad protection against SARS coronaviruses

Scientists have discovered a unique class of small antibodies that strongly protect against a variety of SARS coronaviruses, including SARS-COV-1 and numerous early and recent SARS-CoV-2 variants. The unique antibodies target a key highly conserved site at the base of the virus's spike protein, effectively shutting it down and preventing the virus from infecting cells. The results, published inNature communicationProvide a promising route to developing broad-spectrum antiviral treatments that could remain effective against future viral variants.

SARS-COV-2, the virus behind Covid-19, continues to be a potential threat as it evolves into newer variants that are resistant to currently approved antibody therapies. Resistance arises largely because antibodies typically target virus regions such as the receptor binding domain of the spike protein, which also frequently mutate, allowing escape from antibody recognition.

To address this, a research team led by Prof. Xavier Saelens and Dr. Bert Schepens from the Vib-ugent Center for Medical Biotechnology used a different strategy by focusing on one of the more stable subunits of the spike protein. The so-called S2 subunit is crucial for the virus's ability to fuse with host cells, a process essential for infection, and more is conserved across different coronaviruses.

A molecular clamp on the virus

The team turned to llamas (specifically, a llama named Winter). Llamas produce so-calledSingle domain antibodiesalso known as VHHS or nanobodies, which are much smaller than the antibodies produced by most animals, including humans. The researchers identified several Lama antibodies that potently neutralize a broad group of SARS coronaviruses.

What makes these antibodies particularly promising is their unique mode of action: they act like a molecular clamp. They fold on the poorly exposed, highly conserved region (a coiled coil of 3 alpha helices) at the base of the virus's spike protein. In this way, they lock the spike protein in its original form and physically prevent it from unfolding into the shape of the virus to infect cells.

The antibodies showed strong protection against infections in laboratory animals, even at low doses. And when researchers tried to force the virus to evolve resistance, the virus struggled, producing only rare escape variants that were much less contagious. This suggests a powerful, difficult-to-population treatment option.

This region is so important to the virus that it cannot easily mutate without weakening the virus itself. This gives us a rare advantage: a goal that is both essential and stable for variants. “

Prof. Xavier Saelens, senior author of the study

Better treatments

This discovery marks a significant advance in the search for durable and generally effective antiviral therapies, offering hope for treatments that can keep pace with viral evolution.

“The combination of high potency, broad activity against numerous viral variants and a high resistance barrier is incredibly promising,” adds Saelens. “This work provides a strong foundation for the development of next-generation antibodies that could be critical in combating not only current but also future coronavirus threats.”

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