The virus causing Covid today is not the same virus that first made people sick in December 2019. And by now this is a concept well known to the general public, who have learned what variants are and how important it is to monitor them. Some of those currently in circulation have been found to be partially resistant to some of the antibody-based therapies developed on the basis of the original virus. A team of scientists has addressed the problem and identified an antibody that their studies appear to be “highly protective at low doses against a wide range of viral variants.” The results of their work are published online in ‘Immunity’ magazine. “As the pandemic continues, more variants will inevitably arise and the problem of resistance will only increase,” is the premise on which their research rests. The authors, scholars at the Washington University School of Medicine in St. Louis, focused their attention on an antibody that binds to a part of the virus that differs little between variants, meaning that resistance is unlikely to arise at this point. . The research could pave the way for the development of new antibody-based therapies that are less likely to lose their potency when the virus mutates. “Current antibodies may work against some but not all variants,” said the senior author. of work, Michael S. Diamond. “The virus will likely continue to evolve. Having broadly neutralizing and effective antibodies that work individually and can be paired to create new combinations will likely prevent resistance.” To find neutralizing antibodies that work against a wide range of variants, the researchers started by immunizing the mice with a key part of the Spike protein known as the receptor binding domain (Rbd). Then, they extracted the cells that produce antibodies and got 43 that recognize this part of the Spike. Then they measured how effectively these antibodies were able to prevent cell infection in vitro. Nine of the antibodies that turned out to be the most potent were tested on mice to see if they could protect animals infected with the original virus from the disease. Several antibodies passed both tests, with varying degrees of potency. The scientists selected the two most effective and tested them against the concern variants Alpha, Beta, Gamma and Delta and also on two variants of interest (Kappa and Iota) and several other unnamed ones that are monitored as potential threats. One antibody, SARS2-38, easily neutralized all variants. Additionally, a humanized version of SARS2-38 protected mice against diseases caused by two variants: Kappa and a virus containing the Beta variant spike protein. The Beta variant is notoriously more resistant to antibodies, so its inability to resist SARS2-38 is particularly notable, the researchers noted. The experts didn’t stop there and also pinpointed the precise spot on the spike protein recognized by the antibody by identifying two mutations that could, in principle, prevent the antibody from working. However, these are extremely rare in the real world (in a database of nearly 800,000 Sars-CoV-2 sequences they found them only 0.04%). “This antibody is both highly neutralizing (meaning that it works very well at low concentrations) which is largely neutralizing (in the sense that it works against all variants) “, concludes Diamond specifying that this combination is unusual and highly desirable. It also binds to a single spot on the spike protein that is not targeted by other developing antibodies. “We might start thinking about combining this antibody with another that binds somewhere else to create a combination therapy that would be very difficult for the virus to resist,” says the expert.
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