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

Jules B. Weinstein, Timothy A. Bates, Hans C. Leier, Savannah K. McBride, Eric Barklis, Fikadu G. Tafesse

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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

Original languageEnglish (US)
Article number103960
Issue number3
StatePublished - Mar 18 2022


  • Applied microbiology
  • Bioengineering
  • Nanotechnology

ASJC Scopus subject areas

  • General


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