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Researchers have identified an antibody that broadly neutralized all tested SARS-CoV-2 subvariants as well as SARS-CoV-1 in laboratory experiments and several SARS-CoV-2 variants of concern in mice. Because it targets a spike protein area that may be less affected by genetic variations, the newly discovered antibody could better retain potency against emerging SARS-CoV-2 subvariants and future coronaviruses, if developed into therapeutic products.
Most current SARS-CoV-2 therapeutic antibodies work by binding to proteins in the virus receptor binding domain (RBD) that target angiotensin-converting enzyme 2 (ACE2). This blocks the virus from attaching to ACE2 on host cell membranes. But as the virus has evolved, multiple genetic variations have altered the ACE2-binding proteins so much that most current antibodies no longer block them effectively.
By contrast, the recently discovered SW186 antibody binds to an outer RBD region that does not attach to ACE2. That this RBD area was conserved not only as SARS-CoV-2 evolved but also in the related SARS-CoV-1 suggests that it may control an important function likely to be conserved in future variants and SARS coronaviruses.
Researchers found SW186 by isolating a panel of SARS-CoV-2 antibodies from mice immunized with the viral spike protein. Laboratory tests showed that only SW186 and 1 other antibody neutralized all the SARS-CoV-2 variants tested, including HU-1, Alpha, Beta, Delta, Gamma, Lambda, Mu, and Omicron, though its potency against Omicron BA.2.12.1, BA.4, and BA.5 was reduced. SW186 also neutralized SARS-CoV-1.
SW186 greatly reduced SARS-CoV-2 Alpha, Beta, and Delta viral loads in the lungs of mice, and protected the lungs from viral damage and inflammatory cell infiltration. It also prevented body weight loss from the Delta variant.
“Further structure-based engineering of SW186 may lead to development of more broadly effective antibodies against the circulating and future SARS viruses,” the authors wrote in Science Immunology.
Créditos: Comité científico Covid