Vir Biotechnology Announces New Research Demonstrating Novel Mechanisms by Which SARS-CoV-2 Enters Host Cells - Seite 2
When tested in more physiologic conditions, with cells expressing low levels of ACE-2 together with lectin receptors, non-RBM antibodies showed an enhanced ability to block viral infection. S309 (the precursor to VIR-7831 and VIR-7832), which targets a conserved non-RBM site within the RBD, showed enhanced neutralizing activity, reaching 100% neutralization. In contrast, antibodies that target the RBM were less effective in preventing infection. Additionally, a subset of the RBM-targeting antibodies analyzed in the study, including three clinical-stage antibodies, were shown to promote cell-cell fusion driven by the SARS-CoV-2 spike protein, potentially promoting cell-to-cell spread of the infection.
“As we continue to advance research that elucidates the mechanisms of SARS-CoV-2 infection, including the development of the disease and immunity to infection, one consistent finding of this study appears to be that certain classes of mAbs have potential advantages at blocking auxiliary receptor-enhanced infection,” said Herbert “Skip” Virgin, M.D., Ph.D., chief scientific officer of Vir. “These data, together with recent studies showing an 85% reduction in hospitalization and death in high-risk outpatients receiving VIR-7831 compared to placebo and promising performance against SARS-CoV-2 variants in the lab, add to the growing body of evidence suggesting that antibodies that bind to a conserved non-RBM site of the virus are well suited to help treat and/or prevent COVID-19 infection and have the potential to address both current and future mutations.”
VIR-7831 and VIR-7832 are investigational compounds, not approved by the U.S. Food and Drug Administration or any other regulatory authority.
VIR-7831 is an investigational dual-action SARS-CoV-2 monoclonal antibody. Preclinical data suggest it has the potential to both block viral entry into healthy cells and clear infected cells. The antibody binds to an epitope on SARS-CoV-2 that is shared with SARS-CoV-1 (the virus that causes SARS), indicating that the epitope is highly conserved, which may make it more difficult for resistance to develop. VIR-7831, which incorporates Xencor’s Xtend technology, also has been designed to achieve high concentration in the lungs to ensure optimal penetration into airway tissues affected by SARS-CoV-2 and to have an extended half-life.
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