The Llama, the Hamster, and a New Path for Covid Treatment

For decades, mice, monkeys, and roundworms have been the workhorses of science—“model organisms,” in academic parlance—and for good reason. After generations of research, scientists have a solid grasp on their genetics, physiology, and behavior, which makes it possible to study them in unparalleled detail. But some projects require something a bit more unique. To design a new potential Covid treatment, researchers at the Rosalind Franklin Institute at Oxford University took advantage of the biological quirks of an unlikely animal pair: the llama and the Syrian hamster.Though llamas aren’t exactly common tools for scientific research, their utility is well established: Like humans and other animals, they produce molecules called antibodies to recognize invaders and defeat infections, but their antibodies are unusually small. These “nanobodies” are far easier to manufacture in the lab than human antibodies, which makes them particularly useful for research and, potentially, clinical applications . “It seems to me that anything a human antibody can do, a nanobody could, in theory, do the same thing as well,” says Jiandong Huo, a postdoctoral researcher at Oxford who led this study.Last year, Huo and his colleagues published a paper showing that they had generated nanobodies that could neutralize SARS-CoV-2 , the virus that causes Covid-19. These lab-made nanobodies blocked the virus from infecting cells in the test tube, but the team knew that the llama’s immune system would do even better.So they embarked on the far more time-consuming task of injecting a llama with the SARS-CoV-2 spike protein and waiting for it to generate its own novel nanobodies against the invader. Their patience was rewarded: These new nanobodies did a much better job of blocking the spike protein from attaching to the ACE2 receptor , the protein through which the virus accesses the cell. “They’re about 1,000 times more potent,” says James Naismith, professor of structural biology at Oxford University and a senior author on both studies.Studying these nanobodies in the test tube wasn’t enough to prove that they could successfully fight Covid, so Naismith and his colleagues moved from llamas to another animal with some convenient biology. Syrian, or golden, hamsters, which weigh about five times as much as the dwarf hamsters typically kept as pets, have also been used as research animals for a long time, but they are astonishingly well suited to the current moment—unlike most other small animals, they are susceptible to SARS-CoV-2. Through some strange biological happenstance, the hamster ACE2 receptor looks a lot like the human receptor. So when Huo and his colleagues obtained promising nanobodies from the llama, they were able to infect hamsters with the virus and see whether the nanobodies successfully fought it off.The results, published last Wednesday in the journal Nature Communications, showed that hamsters who received a dose of one of those nanobodies 24 hours after being infected with SARS-CoV-2 returned to their pre-Covid weights just a few days later, a sign that they were beating the virus. Untreated control animals continued to lose weight. The treated hamsters also showed significantly less evidence of lung infection. And because nanobodies are so small and so stable, the researchers didn’t even have to inject the treatment, as is necessary for a human-derived antibody—the nanobodies were sprayed directly into the hamsters’ nostrils.The 24-hour delay between infection and nasal spray has important implications for the potential use of this nanobody as a Covid treatment, says Ray Owens, professor of molecular biology at Oxford and the studies’ other senior author. Once SARS-CoV-2 has entered the animal’s cells and started producing more copies of itself, the nanobodies have a much harder job to do in treating the disease. “The fact that you can dampen that down and take it out of the system … it gives you a strong indication of the potential for these sorts of agents as therapeutics,” says Owens.