Nanobodies found in llama blood may offer protection against COVID-19 and its variants, including the ever-evolving omicron strain.

In a paper published in Cell Reports, a team of researchers from the Icahn School of Medicine at Mount Sinai immunized a llama named "Wally" with the SARS-CoV-2 receptor-binding domain (RBD), or the short fragment of the virus that latches onto the protein on the surface of human cells to cause an infection.

The team found that repeated immunization with RBD caused the llama blood to produce nanobodies capable of recognizing SARS-CoV-2 and other coronaviruses, confirming what the researchers referred to as "super-immunity."

From this discovery, the team proceeded to isolate and validate a large repertoire of highly potent antiviral nanobodies effective against a wide range of SARS-like viruses.

"We learned that the tiny size of these nanobodies gives them a crucial advantage against a rapidly mutating virus," said co-author Ian Wilson, PhD, Hansen Professor of Structural Biology and Chair of the Department of Integrative Structural and Computational Biology at Scripps Research in La Jolla, California.

"Specifically, it allows them to penetrate more of the recesses, nooks, and crannies of the virus surface, and thus bind to multiple regions to prevent the virus from escaping and mutating," he added.

Using the new structural information, the team designed an ultrapotent nanobody that can bind to two regions on the RBD of SARS-like viruses, preventing mutational escape.

"While more research is needed, we believe that the broad protection, ultrapotent nanobodies we were able to isolate in the lab can be harnessed for use in humans," said Dr. Yi Shi, PhD, the lead author and associate professor of Pharmacological Sciences and Director of the Center of Protein Engineering and Therapeutics, Icahn School of Medicine at Mount Sinai.

"Winning the race against the current pandemic, as well as future viral outbreaks, will depend on fast development and equitable distribution of an arsenal of cost-effective and convenient technologies," Dr. Shi added.

"We strongly believe that the novel, inhalable, and extremely potent nanobodies we've discovered can meet that demand on a global scale, particularly in developing countries that are most vulnerable to viruses and the lack of therapies to treat them."