Pitt's inhalable anti-COVID nanobodies, inspired by llamas, 'remarkably active' against delta variant: study

Back in May—when concerns about delta variant of COVID-19 were escalating around the world—researchers at the University of Pittsburgh School of Medicine published promising preclinical research on a novel antibody treatment they developed as an inhalable therapy to fight the virus. But they were worried about emerging mutations of the virus, too, so they launched separate studies designed to determine if the drug might be able to tackle those variants, including delta.

Now they have evidence that the drug and other treatments like it can disarm the virus using one of three possible strategies, making them “remarkably effective” against COVID-19 variants, they said in a statement. They reported their findings in the journal Nature Communications.

The drugs the Pitt team is developing are known as “nanobodies.” They’re tiny fragments of antibodies that occur naturally in llamas and other members of the camelid family. Last year, the researchers announced that they generated nanobodies against COVID-19 by immunizing a llama with the spike protein of SARS-CoV-2, the virus behind the pandemic. They went on to test the most potent nanobody in hamsters, and found it could clear the virus from the lungs in 10 days.

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For the new study, the Pitt researchers worked with a team at Case Western Reserve University to study how eight of the most potent nanobodies they isolated interact with SARS-CoV-2, and how variants affect those interactions. They used a high-resolution imaging technology called cryoelectron microscopy to record the interactions.

They observed that the nanobodies used three pathways to thwart COVID variants. One group interacted with a binding site on healthy cells to prevent the spike protein from attaching to the cell, thus preventing the virus from entering. A second group of nanobodies bound to part of the spike protein that seems to stay constant across SARS-CoV-2 and all its variants, as well as other coronaviruses, giving the drugs the ability to broadly neutralize many iterations of virus. And the third group targeted a region of spike that’s inaccessible to larger antibodies, preventing entry to healthy cells.

Nanobodies could offer several advantages over larger antibodies being used or studied to fight COVID-19. In the May study in hamsters, the Pitt researchers showed that tiny doses of one of the nanobodies they isolated could be given as an inhalation in the nose. That could make it easier to administer than monoclonal antibodies such as Regeneron’s REGEN-COV, which has to be given by IV infusion or injection.

Several other research groups have reported progress developing nanobody treatments for COVID-19. They include Twist Bioscience, the University of Bonn and the University of California, San Francisco.

Pitt’s Yi Shi, Ph.D., assistant professor of cell biology and senior author of the new paper, said in a statement that understanding all the “vulnerabilities and ways to thwart SARS-CoV-2 and coronaviruses in general has huge potential. It will not only help our team select and refine nanobodies to treat and prevent COVID-19, but it also may lead to a universal vaccine, preventing not just COVID-19, but SARS, MERS and other diseases caused by coronaviruses.”