Potent neutralization of clinical isolates of SARS-CoV-2 D614 and G614 variants by a monomeric, sub-nanomolar affinity nanobody

Sci Rep. 2021 Feb 8;11(1):3318. doi: 10.1038/s41598-021-82833-w.

Abstract

Despite unprecedented global efforts to rapidly develop SARS-CoV-2 treatments, in order to reduce the burden placed on health systems, the situation remains critical. Effective diagnosis, treatment, and prophylactic measures are urgently required to meet global demand: recombinant antibodies fulfill these requirements and have marked clinical potential. Here, we describe the fast-tracked development of an alpaca Nanobody specific for the receptor-binding-domain (RBD) of the SARS-CoV-2 Spike protein with potential therapeutic applicability. We present a rapid method for nanobody isolation that includes an optimized immunization regimen coupled with VHH library E. coli surface display, which allows single-step selection of Nanobodies using a simple density gradient centrifugation of the bacterial library. The selected single and monomeric Nanobody, W25, binds to the SARS-CoV-2 S RBD with sub-nanomolar affinity and efficiently competes with ACE-2 receptor binding. Furthermore, W25 potently neutralizes SARS-CoV-2 wild type and the D614G variant with IC50 values in the nanomolar range, demonstrating its potential as antiviral agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / immunology
  • Animals
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology*
  • Antibody Affinity / genetics*
  • COVID-19 / immunology*
  • COVID-19 / virology
  • Camelids, New World / immunology
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Green Fluorescent Proteins / genetics
  • HeLa Cells
  • Humans
  • Immunization
  • Male
  • Neutralization Tests
  • Peptide Library
  • Protein Binding / genetics
  • SARS-CoV-2 / chemistry
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / isolation & purification
  • Single-Domain Antibodies / immunology*
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology*
  • Transfection

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Peptide Library
  • Single-Domain Antibodies
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Green Fluorescent Proteins
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2