The Llama, the Hamster, and a New Approach to the Treatment of Covid

The Oxford team originally identified four different llama nanobodies as promising candidates, but they only tested one on hamsters: C5, which blew last year’s options out of the water. “It’s among the best in the field,” said Phillip Pymm, a postdoctoral researcher at the Walter and Eliza Hall Institute of Medical Research who was not involved in this study.

Oxford researchers aren’t sure why C5 works so well, but they have a theory. Unlike many other nanobodies, C5 binds to the “all down” configuration of the SARS-CoV-2 spike protein, which does not infect cells, and prevents them from transferring to an infectious pathogen. -ayo. By essentially shutting down spike proteins in this inactive state, C5 can provide a much higher level of protection. “C5 is absolutely a dead stone virus,” Naismith said. (To make the nanobodies as powerful as possible, they used a “trimer” – three copies of it put together.) And, according to him, he and his tem have an upcoming work showing that the C5 just as effective against the Delta race.

Back in May, a team from the University of Pittsburgh demonstrated that their own origin of the llama nanobody could also restrain and treat Covid in hamsters when administered by nasal spray. Like the treated hamster in the Oxford study, these animals lost less weight after infection and had less virus in their lungs than their untreated counterpart.

For Paul Duprex, a professor of microbiology and molecular genetics at the University of Pittsburgh and one of the study’s oldest authors, expanding the menu of Covid-treated nanobodies represents a significant advancement. “What we’re really excited about is the use of combinations of different antibodies as a mechanism to overcome the differences,” he said. Imagine a variety of nanobodies being served as a cocktail; if a viral mutation prevents a nanobody from binding, others may be compensated.

But despite their unusual biological resemblance to ours on the one hand, hamsters are far from human. They’re much smaller, for one thing, and Covid grows them faster. C5 and other nanobodies still have a long way to go before they can be used to treat humans-there is no guarantee that what hamsters will do will prove successful in humans. “The proof of the pudding is in the food,” Duprex said. “Let’s see where it goes.” And we don’t know immediately; the human clinical trial process is rigorous and time consuming.

However, the successful hamster experiments represent a major step forward from the work of the llama nanobody by the Oxford team last summer. They are already excited to think about what nanobodies might mean for the treatment of respiratory diseases. Because it can be administered intranasally, a person who is positive for Covid can – in theory – get treatment quickly and easily at home. Naismith imagines that a person who enters a hazardous environment, such as a nursing home or hospital, can protect themselves from infection by taking a preventative dose.

And sprays have another significant advantage – they go directly into the airway. “It really targets the area of ​​infection in respiratory diseases like Covid,” Pymm said. With nanobodies that protect the throat and lungs, Covid may never take control of a person’s body.

While making llama nanobodies is slow when llamas do it, they can be easily synthesized by yeast and bacteria-and they don’t require sophisticated storage like human antibodies do. “Nanobodies are much more robust, and they can survive even at hot temperatures,” Huo said, meaning they may be easily delivered in low -income regions, where the issue of cooling can be an issue.

The Oxford team has asked to start running human clinical trials soon, but they also hope that, by the time any treatment is approved, vaccines and other measures will end the pandemic. Even if these nanobodies are not used in Covid treatment, Naismith said their findings could still be valuable. “We can pass clinical trials and get the accumulated knowledge, so that when the next thing comes up – the next respiratory illness – just know the road map,” he said.

During future pandemics, lab -made nanobodies could work as a stopgap measure. until vaccines can be passed. “We don’t get to vaccinations much faster than we get to – it’s always been a few months,” Naismith said. “Nanobodies can be faster than vaccines, at least at that stage.”

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