Discovery of Nanosota-2, -3, and -4 as super potent and broad-spectrum therapeutic nanobody candidates against COVID-19

J Virol. 2023 Nov 30;97(11):e0144823. doi: 10.1128/jvi.01448-23. Epub 2023 Oct 19.


The COVID-19 pandemic exposed limitations of conventional antibodies as therapeutics, including high cost, limited potency, ineffectiveness against new viral variants, and primary reliance on injection-only delivery. Nanobodies are single-domain antibodies with therapeutic potentials. We discovered three anti-SARS-CoV-2 nanobodies, named Nanosota-2, -3, and -4, from an immunized alpaca. Nanosota-2 is super potent against prototypic SARS-CoV-2, Nanosota-3 is highly potent against the omicron variant, and Nanosota-4 is effective against both SARS-CoV-1 and SARS-CoV-2. In addition to their super potency and combined broad antiviral spectrum, these nanobodies are cost-effective, can be easily adapted to new viral variants through phage display, and can potentially be administered as inhalers. The Nanosota series are powerful therapeutic candidates to combat circulating SARS-CoV-2 and prepare for possible future coronavirus pandemics.

Keywords: ACE2; SARS-CoV-1; SARS-CoV-2; animal model; cryo-EM; omicron; receptor-binding domain; single-domain antibody from camelids; spike protein; virus neutralization.

MeSH terms

  • Antibodies, Neutralizing
  • Antibodies, Viral / therapeutic use
  • COVID-19* / therapy
  • Humans
  • Pandemics
  • SARS-CoV-2*
  • Single-Domain Antibodies* / pharmacology
  • Spike Glycoprotein, Coronavirus


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Single-Domain Antibodies
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants