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By combining nanobodies targeting different regions of the SARS-CoV-2 Spike protein, the researchers were able to protect cells against infection.
Researchers have developed combination nanobodies that can neutralize SARS-CoV-2, even if it mutates. According to the team, the nanobodies could be developed as a drug therapy to use in people with severe COVID-19, the disease caused by SARS-CoV-2, or in people who may not like the immunocompromised.
Nanobodies are small fragments of antibodies, also known as single domain antibodies (sdAb), produced by camels such as alpacas, llamas and camels. Some believe they can do better treatments than full-sized antibodies because they are significantly smaller, more stable, and easier to produce cost effectively on a large scale.
The binding of Spike (S) proteins on the surface of the SARS-CoV-2 coronavirus to angiotensin-converting enzyme 2 (ACE2) receptors on human cells is what allows the virus to enter human cells . Therefore, scientists suggest that preventing this interaction could prevent infection.
In a new study, researchers at the Swedish Karolinska Institute, in collaboration with researchers at the University of Bonn, Germany, and the Scripps Research Institute, United States, generated and screened nanobodies for their ability to inhibit the interaction between SARS-CoV-2 S protein and ACE2. They identified four with an exceptional ability to block the virus’s ability to spread among cultured human cells, then worked to combine them to create new structures that would continue to neutralize the virus even if it mutates.
“What is unique here is that we have assembled nanobodies that bind to two different places on the S protein of the virus,” explained one of the study’s corresponding authors, Martin Hällberg, researcher at the Department. of cellular and molecular biology at Karolinska Institute. “This variant combination binds better than individual nanobodies and is exceptionally effective at blocking the ability of the virus to spread between human cells in cell culture.”
Additionally, the combined nanobodies worked even when tested on a virus variant that mutates extremely quickly. “This means that the risk is very low that the virus will become resistant to these combined nanobodies,” Hällberg noted.
He said his ‘favorite’ nan person was llama because ‘it binds directly to the surface where the virus binds to the host cell ACE2 receptor’ and also contains a number of essential amino acids for binding. with ACE2. Because of this similarity to ACE2, the virus is unlikely to mutate enough to develop resistance to this nanobody while retaining its ability to interact with ACE2. Hällberg also revealed that during their experiments, the SARS-CoV-2 virus never managed to mutate enough to escape one of their combinations, in which this nan-person Llama was linked to that of a alpaca.
Dioscure Therapeutics, a spin-off company of the University of Bonn, will perform further testing on the nanobodies in clinical trials. Meanwhile, researchers at the Karolinska Institute will attempt to improve the ability of combined nanobodies to bind together by altering the individual building blocks of nanobodies.
The study was published in Science.
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