A serum-stable RNA aptamer specific for SARS-CoV-2 neutralizes viral entry

Julian Valero*, Laia Civit, Daniel M. Dupont, Denis Selnihhin, Line S. Reinert, Manja Idorn, Brett A. Israels, Aleksandra M. Bednarz, Claus Bus, Benedikt Asbach, David Peterhoff, Finn S. Pedersen, Victoria Birkedal, Ralf Wagner, Søren R. Paludan, Jørgen Kjems*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

67 Citations (Scopus)

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created an urgent need for new technologies to treat COVID-19. Here we report a 20-fluoro protected RNA aptamer that binds with high affinity to the receptor binding domain (RBD) of SARS-CoV-2 spike protein, thereby preventing its interaction with the host receptor ACE2. A trimerized version of the RNA aptamer matching the three RBDs in each spike complex enhances binding affinity down to the low picomolar range. Binding mode and specificity for the aptamer–spike interaction is supported by biolayer interferometry, single-molecule fluorescence microscopy, and flow-induced dispersion analysis in vitro. Cell culture experiments using virus-like particles and live SARS-CoV-2 show that the aptamer and, to a larger extent, the trimeric aptamer can efficiently block viral infection at low concentration. Finally, the aptamer maintains its high binding affinity to spike from other circulating SARS-CoV-2 strains, suggesting that it could find widespread use for the detection and treatment of SARS-CoV-2 and emerging variants.

Original languageEnglish
Article numbere2112942118
JournalProceedings of the National Academy of Sciences (PNAS)
Volume118
Issue50
Number of pages10
ISSN0027-8424
DOIs
Publication statusPublished - Dec 2021

Keywords

  • Aptamer multimerization
  • Aptamer selection
  • SARS-CoV-2 targeting
  • Spike protein
  • Viral neutralization

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