April 8, 2021 -- Vir Biotechnology touted a preclinical study that highlights the mechanisms SARS-CoV-2 uses to enter host cells and identifies three new auxiliary receptors that may affect the clinical efficacy of the company's investigational monoclonal antibodies (mAbs).
A growing body of evidence suggests mAbs that target a conserved epitope could be highly effective against SARS-CoV-2 and associated known mutations, according to the company. Prior research has shown that SARS-CoV-2 infection is mediated by the virus binding to the angiotensin-converting enzyme 2 (ACE2) entry receptor. Vir has developed two non-receptor binding motif (RBM)-targeting antibodies, VIR-7831 and VIR-7832, that target a conserved non-RBM site within the receptor binding domain (RBD).
Findings from the new research highlight the importance of three additional auxiliary receptors that enhance infection mediated by the ACE2 receptor. The study looked at the role of DC-SIGN and L-SIGN lectins in infection and further identified the SIGLEC1 lectin as a new participant in infection.
These auxiliary receptors also play an important role in modulating the neutralizing activity of different classes of spike-specific antibodies and may contribute to viral dissemination in the most severe COVID-19 cases, the company said. When tested in more physiologic conditions, with cells expressing low levels of ACE2 together with lectin receptors, non-RBM antibodies showed an enhanced ability to block viral infection, according to Vir.
Vir said the observation indicates the significant limitations of the use of cells overexpressing ACE2 for studies of mAbs and measuring serum neutralizing antibodies elicited by vaccination or infection.