The Oxford University team initially identified four different llama nanobodies as promising candidates, but they only tested one in hamsters: C5, which made last year’s choice stand out from the water. “It’s the best in the field,” said Philip Pim, a postdoctoral researcher at the Walter and Eliza Hall Institute of Medical Research, who was not involved in the study.
Researchers at Oxford University are not sure why C5 is so effective, but they do have a theory. Unlike many other Nanobodies, C5 binds to the “fully closed” configuration of the SARS-CoV-2 spike protein, which is unable to infect cells and prevents them from entering the infectious configuration. By essentially locking the spike protein in this inactive state, C5 can provide a particularly high degree of protection. “C5 is definitely the death killer of the virus,” Naismith said. (In order to make Nanobodies as effective as possible, they used a “trimer”-three copies of it joined together.) And, he said, the upcoming work of him and his team proves that C5 changes Delta. The body is equally effective.
Back in May, a team from the University of Pittsburgh proved that their own llama-derived nanobody can also Prevention and treatment of Covid In hamsters, it is administered by nasal spray. Like the treated hamsters in the Oxford study, these animals lost the least weight after infection and had far fewer lung viruses than their untreated counterparts.
Paul Duprex, professor of microbiology and molecular genetics at the University of Pittsburgh and one of the senior authors of the study, believes that expanding the menu of nanobodies that can treat the new coronavirus is an important advancement. “What we are really excited about is using a combination of different antibodies as a mechanism to overcome mutation,” he said. Imagine various Nanobodies administered in the form of a cocktail; if viral mutations prevent the binding of one Nanobody, other Nanobodies may compensate.
However, despite their unusual biological similarities with us in one aspect, hamsters are far from humans. On the one hand, they are much smaller, and Covid is making faster progress in them. C5 and other nanobodies have a long way to go before they can be used to treat humans-there is no guarantee that what works in hamsters will succeed in humans. “The proof of pudding is eating,” Duprex said. “Let’s see where it went.” We won’t know immediately; the human clinical trial process is rigorous and takes time.
Nevertheless, the successful hamster experiment represents a big step forward for the Oxford team’s llama nanobody work last summer. They are already excited about the significance of Nanobodies for the treatment of respiratory diseases. Since they can be administered intranasally, in theory, people who test positive for Covid can receive treatment quickly and easily at home. Naismith imagines that if someone is about to enter a high-risk environment, such as a nursing home or hospital, they can protect themselves from infection by taking a preventive dose.
Sprays have another important advantage-they enter the airway directly. “It actually targets the infected parts of respiratory diseases such as Covid,” Pim said. With nanobodies protecting the throat and lungs, Covid may never be able to control someone’s body.
Although the production of llama nanobodies is slow when llamas do this, they can be synthesized cheaply and easily in yeast and bacteria – and they don’t require the complicated storage of human antibodies. “Nanobodies are stronger and can be stored even at warm temperatures,” Huo said, which means they may be easier to distribute to low-income areas, where refrigeration may be a problem.
The Oxford team hopes to begin human clinical trials as soon as possible, but they also hope that by the time any treatment may be approved, vaccines and other measures have ended the pandemic. Even though these nanobodies have never been used to treat Covid, Naismith said the knowledge they have learned is still valuable. “We will pass clinical trials and gain accumulated knowledge so that when the next thing happens-the next respiratory disease-then we know the road map,” he said.
During future pandemics, nanobodies produced in the laboratory may be used as a stopgap measure Until the vaccine can be launchedNaismith said: “Our vaccine development speed cannot be much faster than in the past-they always take months.” “Nanobodies may be faster than vaccines, at least in the early stages.”
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