Roundworms, monkeys, and mice have been the backbone of sciencemodel organisms for decades. Scientists have developed a deep understanding of their biology, genetics, and behavior over many generations. This allows them to be studied in unprecedented detail. Some projects are more challenging. Researchers at Oxford University's Rosalind Franklin Institute used the unique biological characteristics of a rare animal pair to design a new Covid treatment.
Although llamas may not be a common tool for scientific research, their utility has been established. They produce molecules called antibodies, which can recognize invaders and defeat them. However, their antibodies are uncommonly small. Nanobodies are much easier to make in the laboratory than human antibodies. This makes them especially useful for research and potentially clinical applications. Jiandong Huo, an Oxford postdoctoral researcher, said that nanobodies could theoretically do anything a human antibodies can do.
Huo and his coworkers published a paper last year demonstrating that nanobodies could be created to neutralize SARSCoV-2, which is the virus responsible for Covid-19. The virus was not able to infect cells in the test tube with these nanobodies, but the team knew the llama's immune system would be more effective.
They then set about the more tedious task of injecting a llama infected with the SARS/CoV-2 spike protein, and then waiting for the virus to create its own nanobodies. They were rewarded for their patience: The new nanobodies blocked the spike protein's attachment to the ACE2 receptor. This is the protein that the virus can access the cell. James Naismith, Oxford University professor of structural biology and senior author of both studies, said that they are about 1,000 times more powerful.
These nanobodies were not enough to show that they can fight Covid. So Naismith and his collaborators switched from llamas to an animal with a more convenient biology. The golden or Syrian hamsters weigh five times more than dwarf hamsters and are used as research animals. However, unlike most small animals, they are highly susceptible to SARS-CoV-2. The hamster ACE2 receptor is very similar to the human receptor, due to some bizarre biological coincidence. Huo and his associates obtained promising nanobodies form the llama and were able infect hamsters. They could then test whether the nanobodies had beaten it off.
Nature Communications published the results last Wednesday. They showed that hamsters that received one of the nanobodies within 24 hours of being infected with SARS/CoV-2, returned to their pre-Covid weights a few days later. This was a sign they were fighting the virus. The weight loss in untreated control animals did not stop. The lung infections in the treated hamsters were also significantly lower. Because nanobodies are small and stable, researchers didn't have to inject it, which is required for human-derived antibodies. Instead, nanobodies were sprayed into the nostrils of the hamsters.
Ray Owens, professor at Oxford of molecular biology and senior author of the study, said that the 24-hour delay between infection, nasal spray, and ingestion has important implications for the use of the nanobody as a Covid therapy. The nanobodies will have a harder time treating the disease once SARS-CoV-2 is infected with the cells of animals. Owens says that the fact that you can slow down the virus and remove it from the body gives you strong evidence of its potential as a therapeutic agent.
