Slaying SARS-CoV-2 One (Single-domain) Antibody at a Time

Camelid-derived and synthetic single-domain antibodies (sdAbs) are emerging as potent weapons against the novel coronavirus, SARS-CoV-2. sdAbs are small, compact, thermostable immunoglobulin elements capable of binding targets with subnanomolar affinities. By leveraging the power of phage- and yeast surface-display technologies, rare sdAbs can be isolated from highly diverse and complex antibody libraries. Once in hand, sdAbs can be engineered to improve binding affinity, avidity, target specificities, and biodistribution. In this Opinion piece we highlight a series of sophisticated studies describing the identification of ultrapotent sdAbs directed against the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. We discuss the possible applications of these antibodies in the global fight against COVID-19.