A potent alpaca-derived nanobody that neutralizes SARS-CoV-2 variants

The 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 nobulization, making it an excellent candidate for further development into a therapeutic approach for COVID-19.

Automated summary

Researchers have identified an alpaca-derived antibody fragment, saRBD-1, that can competitively bind to the receptor-binding domain of the spike protein in SARS-CoV-2, thus disrupting the virus's ability to infect human cells. They have also developed a bivalent nanobody construct that can block infection at very low concentrations and remains effective against emerging variants of the virus.