Single-domain antibodies make a difference

Abstract

A double hit with one antibody construct may avoid viral escape The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, mediates attachment of the virion to the host cell, binding to the receptor, and fusion of the viral and host cell membranes. This releases the viral genomic RNA into the host cell cytoplasm, which is the start of virus replication. Antibodies that interfere with SARS-CoV-2 spike function—in particular, antibodies that prevent the interaction between the receptor binding domain (RBD) of spike and human angiotensin-converting enzyme 2 (ACE2), the canonical receptor on the host cell surface—can neutralize the virus in vitro and are associated with protection from infection in vivo (1). On page 691 of this issue, Koenig et al. (2) describe four SARS-CoV-2–neutralizing single-domain antibodies, or VHHs, and combinations thereof that can disable spike function. This extends the growing list of reports on SARS-CoV-2 spike–specific single-domain antibodies that have been proposed as potential therapeutics for COVID-19 patients.