Against the Conservatives
A universal neutralizing antibody has been created for the treatment of coronavirus infections
Georgy Chistov, PCR.news
COVID-19 has already claimed more than 5 million lives, and people continue to get sick and die, despite the fact that several effective vaccines have been created during the pandemic. They are available all over the world, but immunization is too slow to keep the virus under control. SARS-CoV-2 is constantly mutating, eluding immunity. Therefore, the attention of scientists, among other things, is focused on neutralizing antibodies against the conservative part of the S-protein and the creation of universal therapy for coronavirus infections.
The SARS-CoV-2 S protein has two non-covalently bound domains: S1, which often changes its amino acid composition, and the highly conserved S2. Scientists from the University of Alabama at Birmingham (USA), with the support of Aridis Pharmaceuticals Inc., isolated B cells from the plasma of patients who had been ill, which synthesize antibodies to the S2 domain. They managed to do this thanks to two fluorescently labeled recombinant proteins. One of them contains only the S2 domain (S2-STBL), and the other contains a combination of S1 protein from SARS-CoV and S2 from SARS—CoV-2 (SARS-CoV1/2). The B cells associated with these proteins were sorted using cytofluorimetry.
As a result, 17 recombinant IgG1 antibodies were created. The researchers did not observe activity against S1 protein in these antibodies, but some of them actively bound to the S2 domain of commercial production, as well as to S2-STBL and the chimeric protein SARS-CoV1/2. Eight antibodies were able to neutralize the pseudovirus, and half of them were effective against live coronavirus, including the delta strain. Interestingly, the 1249A8 antibody had a more powerful neutralizing activity than the existing CV3-25 antibody, which is also specific to the S2 domain. As further experiments showed, 1249A8 bound to the same epitope as CV3-25 and activated a more active antibody-dependent phagocytosis.
1249A8 successfully protected mice from SARS-CoV2 infection. In low concentrations, this antibody helped reduce weight loss in infected mice and saved 60% of the animals from death. In the negative control, the entire cohort of mice died. Increasing the antibody concentration helped to completely prevent mortality and weight loss. In addition, the introduction of the antibody reduced lung damage and reduced viral load in them.
Given the high conservativeness of the S2 domain among coronaviruses, the researchers decided to test the effectiveness of 1249A8 on neutralizing various pathogen variants. To the surprise of the authors, the new antibody successfully neutralized 5 types of coronavirus. Unlike CV3-25, the 1249A8 antibody was able to neutralize MERS-CoV and was more effective against SARS-CoV. With respiratory administration, 1249A8 also demonstrated efficacy against the wild-type strain (Urbani).
Thus, the researchers developed a monoclonal neutralizing antibody to the conservative part of the S-protein. Unlike existing analogues, the new antibody works effectively against different representatives of the genus betacoronaviruses. This development may be the first step towards the creation of universal drugs for the treatment of coronavirus infections.
Article by Piepenbrink et al. A potential universal beta-coronavirus therapeutic activity mediated by direct respiratory administration of a Spike S2 domain-specific human neutralizing monoclonal antibody is published in the journal PLoS Pathogens.
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