摘要：SummaryThe spike glycoprotein of SARS-CoV-2 engages with human ACE 2 to facilitate infection. Here, we describe an alpaca-derived heavy chain antibody fragment (VHH), saRBD-1, that disrupts this interaction by competitively binding to the spike protein receptor-binding domain. We further generated an engineered bivalent nanobody construct engineered by a flexible linker and a dimeric Fc conjugated nanobody construct. Both multivalent nanobodies blocked infection at picomolar concentrations and demonstrated no loss of potency against emerging variants of concern including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Epsilon (B.1.427/429), and Delta (B.1.617.2). saRBD-1 tolerates elevated temperature, freeze-drying, and nebulization, making it an excellent candidate for further development into a therapeutic approach for COVID-19.Graphical abstractDisplay OmittedHighlights•SARS-CoV-2 variants effectively neutralized by saRBD-1 VHH with picomolar affinity•saRBD-1 neutralization increases when expressed as a bivalent or Fc construct•saRBD-1 binds SARS-CoV-2 RBD as a likely class 1 neutralizing antibody•saRBD-1 retains binding, neutralization after heat and nebulization treatmentsApplied microbiology; Bioengineering; Nanotechnology
