Inhaled Nanobodies Effective Against COVID-19

In a paper published today in Science Advances, researchers from the University of Pittsburgh School of Medicine showed that inhalable nanobodies targeting the spike protein of the SARS-CoV-2 coronavirus can prevent and treat severe COVID-19 in hamsters. This is the first time the nanobodies–which are similar to monoclonal antibodies but smaller in size, more stable and cheaper to produce–were tested for inhalation treatment against coronavirus infections in a pre-clinical model.

The scientists showed that low doses of an aerosolized nanobody named Pittsburgh inhalable Nanobody-21 (PiN-21) protected hamsters from the dramatic weight loss typically associated with severe SARS-CoV-2 infection and reduced the number of infectious virus particles in the animals’ nasal cavities, throats and lungs by a million-fold, compared to placebo treatment with a nanobody that doesn’t neutralize the virus.

By using an inhalation therapy that can be directly administered to the infection site–the respiratory tract and lungs–we can make treatments more efficient,” said co-senior author Yi Shi, Ph.D., assistant professor of cell biology at Pitt. “We are very excited and encouraged by our data suggesting that PiN-21 can be highly protective against severe disease and can potentially prevent human-to-human viral transmission.

Previously, Shi and colleagues discovered a large repertoire of over 8,000 high-affinity SARS-CoV-2 nanobodies. From this repertoire, the scientists selected an ultrapotent nanobody (Nb21) and bioengineered it into a rimeric form to further maximize its antiviral activity. The resulting PiN-21 is by far the most potent antiviral nanobody that has been identified, according to the researchers’ review of published studies.