A serum-stable RNA aptamer specific for SARS-CoV-2 neutralizes viral entry.
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 2'-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.
Mesh Terms:
Angiotensin-Converting Enzyme 2, Aptamers, Nucleotide, Humans, Mutation, Neutralization Tests, Nucleic Acid Conformation, Protein Binding, Protein Interaction Domains and Motifs, SARS-CoV-2, SELEX Aptamer Technique, Spike Glycoprotein, Coronavirus, Virus Internalization
Angiotensin-Converting Enzyme 2, Aptamers, Nucleotide, Humans, Mutation, Neutralization Tests, Nucleic Acid Conformation, Protein Binding, Protein Interaction Domains and Motifs, SARS-CoV-2, SELEX Aptamer Technique, Spike Glycoprotein, Coronavirus, Virus Internalization
Proc Natl Acad Sci U S A
Date: Dec. 14, 2021
PubMed ID: 34876524
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