A new way of treating llamas, hamsters and covids

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

Oxford researchers aren’t sure why C5 works so well, but they have a theory. Unlike many other nanobodies, the C5 SARS-CoV-2 spike is bound to the “all down” configuration of the protein, which is unable to infect the cell and prevents it from entering the infectious configuration. Basically by locking the spike protein in this inactive state, C5 can provide a particularly high level of protection. “C5 is absolutely a stone-dead killer of the virus,” Nicemith says. (To make the nanobodies as powerful as possible, they used a “trimmer” – three copies of which were tied together.) And, he said, he and his team have upcoming work that shows that the C5 is just as effective as the Delta variant.

In May, a team from the University of Pittsburgh showed that nanobodies derived from their own llamas could prevent and treat hamsters with cod. Like the hamsters treated in the Oxford study, these animals lost minimal weight after infection and had far fewer viruses in their lungs than their untreated counterparts.

For Paul Duprex, a professor of microbiology and molecular genetics at the University of Pittsburgh and a senior author of that study, the expansion of the menu of nanobodies that can treat covids represents a significant advance. “What we’re really excited about is using a combination of different antibodies as a process of overcoming diversity,” he said. Imagine different nanobodies operating as a cocktail; If a viral mutation prevents a nanobody from binding, others may be able to compensate.

But on the one hand, despite their unusual biological similarities with us, hamsters are far from human. These are much smaller, for one thing, and Kovid moves faster among them. 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 works in hamsters will prove successful in humans. “There’s evidence of pudding in eating,” Duprex says. “Let’s see where it goes.” And we may not know immediately; The human clinical trial process is rigorous and time consuming.

Nonetheless, successful hamster trials represent a major step forward from the Oxford team’s Lama Nanobody work last summer. They are already temporarily excited about what nanobody means for the treatment of respiratory illnesses. Since they can be administered intravenously, a person who can test positive for covid – theoretically – can get treatment at home quickly and easily. Nicemith imagines that anyone entering a high-risk environment, such as a nursing home or hospital, could protect themselves from infection by taking preventative doses.

And sprays have another important advantage – they go directly into the airways. “It actually targets the site of infection in respiratory diseases like covid,” Pimm says. With nanobodies protecting the throat and lungs, covids will never be able to occupy anyone’s body.

While llama nanobody production is slow when llamas do, they can be cheap and easily synthesized into yeast and bacteria – and they don’t require sophisticated storage like human antibodies. “Nanobodies are more powerful, and they can be kept even at warmer temperatures,” Huo said, meaning they could probably be more easily distributed in low-income areas, where freezing could be a problem.

The Oxford team hopes that people will soon begin moving through clinical trials, but they also hope that vaccines and other measures will already put an end to the epidemic by the time any treatment is approved. Even if these nanobodies were never used to treat covid, Nicemith says what they have learned will still be valuable. “We will go through the clinical trials and get that accumulated knowledge, so that when the next thing comes – the next respiratory disease – we know the road map,” he said.

During future epidemics, lab-generated nanobodies could serve as a potential stopgap measure until vaccines can be introduced. “We can’t go any faster than we gave the vaccines – they’re always going to be a few months,” Nicemith said. “Nanobodies can be faster than vaccines, at least in those early stages.”

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