research topics

ReconnAbs: Receptor-blocking conserved
non-neutralizing antibodies

The discovery of broadly neutralizing coronavirus antibodies has been challenging. For SARS-CoV-2, most neutralizing activity comes from antibodies that target the receptor binding domain (RBD) or N-terminal domain (NTD) of the SARS-CoV-2 spike protein. The RBD and NTD regions are not highly conserved within related coronavirus spike proteins. There are, however, large, conserved epitopes within the spike protein (Fig. 5 – left, blue). No potent neutralizing antibodies have been found against these epitopes. Indeed, these epitopes are generally the target of non-neutralizing antibodies.

We have generated receptor-blocking conserved non-neutralizing Antibodies (ReconnAbs), which are able to convert these non-neutralizing, cross-reactive antibodies into broad spectrum inhibitors by fusion to an RBD-directed neutralizing component (Fig. 5 – right). By targeting highly-conserved epitopes, ReconnAbs show potent activity against all SARS-CoV-2 variants of concern (VOCs), including Omicron, and are likely to retain their activity against future VOCs. We envision that ReconnAbs as a new class of potent, broad-spectrum anti-viral agents.

PUBLIcation highlights

Converting non-neutralizing SARS-CoV-2 antibodies targeting conserved epitopes into broad-spectrum inhibitors through receptor blockade. (PDF) (Nat. Chem. Bio.)
Payton A.-B. Weidenbacher, Eric Waltari, Izumi de los Rios Kobara, Benjamin N. Bell, John E. Pak, Peter S. Kim. Nature Chemical Biology (2022).