Low-Cost Nanobodies from Alpacas are Highly Potent Inhibitors of SARS-CoV-2

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Researchers at the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany, engineered mini-antibodies, called nanobodies, against SARS-CoV-2. The team’s nanobodies are stable up to 95 degrees Celsius (203 F) and are cheaper and less complex to produce than conventional antibodies. So far, the nanobodies have shown impressive efficacy against the virus and its variants in the lab, and the researchers are preparing to conduct a clinical trial to see if they could be a viable treatment for COVID-19 patients.

Two of the newly developed nanobodies (blue and magenta) binding to the receptor-binding domain (green) of the coronavirus spike protein (grey), thus preventing infection with SARS-CoV-2 and its variants.
Credit: Thomas Güttler / Max Planck Institute for Biophysical Chemistry

Antibodies are an important defense against viral invaders in our bodies. These protein structures bind and neutralize a wide variety of pathogens, and are an important part of the immune response generated following vaccination against SARS-CoV-2. They also represent a potential treatment for COVID-19 patients, whereby lab-produced antibodies can be administered to such patients to help them to combat the virus. However, producing antibodies is costly and complex, and it is not currently possible to create enough supplies to treat everyone who needs them.

In contrast, nanobodies, which are more easily manufactured, could be a viable alternative. This latest creation is shaping up to be a promising drug candidate for COVID-19. “For the first time, they combine extreme stability and outstanding efficacy against the virus and its Alpha, Beta, Gamma, and Delta mutants,” said Dirk Görlich, a researcher involved in the study, in a press release.

The three alpaca mares Britta, Xenia, and Nora provided the starting point for the COVID-19 nanobodies.
Credit: Carmen Rotte / Max Planck Institute for Biophysical Chemistry

The Max Planck team use Alpacas to produce the nanobodies by immunizing them against the viral spike protein and then isolating the nanobodies from the blood before further purification and testing. “Our nanobodies originate from alpacas and are smaller and simpler than conventional antibodies,” said Görlich. “The overall burden on our animals is very low, comparable to vaccination and blood testing in humans.”

Strikingly, the new nanobodies have a very high heat tolerance, something that is important for their stability in the body and which can be a sticking point for many biological treatments. “Our nanobodies can withstand temperatures of up to 95 °C without losing their function or forming aggregates,” said Matthias Dobbelstein, another researcher working on the project. “For one thing, this tells us that they might remain active in the body long enough to be effective. For another, heat-resistant nanobodies are easier to produce, process, and store.”      

The researchers are planning a clinical trial of the technology, which may have potential as an inhaled treatment for COVID-19 patients. “Our single nanobodies are potentially suitable for inhalation and thus for direct virus neutralization in the respiratory tract,” said Dobbelstein. “In addition, because they are very small, they could readily penetrate tissues and prevent the virus from spreading further at the site of infection.”

Study in The EMBO Journal: Neutralization of SARS-CoV-2 by highly potent, hyperthermostable, and mutation-tolerant nanobodies

Via: Max Planck Institute for Biophysical Chemistry





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