Llama 'nanobodies’ may yield COVID-19 treatment, Pitt scientists say

Could Wally the llama hold the key to COVID-19?

The immune system of the black-coated animal, who lives on a farm in Massachusetts, was coaxed into producing “nanobodies” — smaller cousins of antibodies — that neutralized the coronavirus in laboratory experiments, University of Pittsburgh scientists reported Thursday.

The potent proteins still are being tested in other animals to gauge their ability to ward off COVID-19, and the Pitt research team had no firm time frame on when they might be tested in humans.

Still the preliminary results, published in Science, suggest that the llama-derived molecules pack a far greater punch than antibodies produced by humans.

“They are orders of magnitude more powerful,” said Yi Shi, assistant professor of cell biology at Pitt’s School of Medicine.

That means they could be given at a far smaller dose, potentially through an inhaler to reach the lungs of an infected patient, the authors said. Synthetic versions of human antibodies, such as those administered to President Donald Trump, are so much larger that the required doses must be given intravenously.

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Zachary Klase, a Drexel University virologist who was not involved with the Pitt research, agreed that it seemed promising. The llama-derived nanobodies bind to the spiky proteins that protrude from each coronavirus particle, apparently interfering with infection in two ways, he said.

In order to penetrate a human cell, these virus spikes must unfold into their upright position, and then latch onto the cell surface. But the nanobodies seem to prevent the spikes from unfolding and also interfere with the mechanism they use to penetrate the cell membrane — almost like gumming up the key to a lock, said Klase, an associate professor in the pharmacology and physiology department at Drexel’s College of Medicine.

“The more functions you block, that’s probably what’s increasing its potency,” he said.

Scientists prompted Wally’s immune system to make the nanobodies by injecting the animal with fragments of the coronavirus. They waited several weeks, drew blood samples, then isolated the nanobodies and grew many more copies for use in experiments, said Pitt researcher Paul Duprex, one of the authors.

Wally was able to remain at the farm, presumably unaware that his proteins were being put to good use.

“That animal’s genetic composition which produces that one nanobody is enough then to take it into the laboratory, completely independent from the llama that can live happily in Massachusetts,” Duprex said.

The Pitt researchers collaborated with Dina Schneidman-Duhovny, a computer scientist at the Hebrew University of Jerusalem.

The idea of deriving a COVID-19 treatment from the llama immune system has been studied at other university labs as well, so far without yielding a treatment. Scientists previously have explored the possibility of using the potent llama proteins against other diseases, including cancer and neurological conditions.