This paper reports the discovery of VHH60, a neutralizing nanobody engineered from a commercially available nanobody. VHH60 effectively competes with human ACE2 for binding to the SARS-CoV-2 spike protein's receptor-binding domain (RBD), inhibiting infection of both ancestral and variant strains in vitro and in vivo. In vivo studies in mice demonstrated superior protection compared to a control nanobody. This work showcases a rapid approach to developing therapeutic nanobodies.
