tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2021 Dec 14;118(50):e2112942118.
doi: 10.1073/pnas.2112942118.
A serum-stable RNA aptamer specific for SARS-CoV-2 neutralizes viral entry
Julián Valero[SUP] 1 2 [/SUP], Laia Civit[SUP] 3 [/SUP], Daniel M Dupont[SUP] 3 [/SUP], Denis Selnihhin[SUP] 4 [/SUP], Line S Reinert[SUP] 5 [/SUP], Manja Idorn[SUP] 5 [/SUP], Brett A Israels[SUP] 3 6 [/SUP], Aleksandra M Bednarz[SUP] 3 6 [/SUP], Claus Bus[SUP] 3 [/SUP], Benedikt Asbach[SUP] 7 [/SUP], David Peterhoff[SUP] 7 [/SUP], Finn S Pedersen[SUP] 4 [/SUP], Victoria Birkedal[SUP] 3 6 [/SUP], Ralf Wagner[SUP] 7 8 [/SUP], Søren R Paludan[SUP] 5 [/SUP], Jørgen Kjems[SUP] 1 2 4 [/SUP]
Affiliations
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 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.
Keywords: SARS-CoV-2 targeting; aptamer multimerization; aptamer selection; spike protein; viral neutralization.
. 2021 Dec 14;118(50):e2112942118.
doi: 10.1073/pnas.2112942118.
A serum-stable RNA aptamer specific for SARS-CoV-2 neutralizes viral entry
Julián Valero[SUP] 1 2 [/SUP], Laia Civit[SUP] 3 [/SUP], Daniel M Dupont[SUP] 3 [/SUP], Denis Selnihhin[SUP] 4 [/SUP], Line S Reinert[SUP] 5 [/SUP], Manja Idorn[SUP] 5 [/SUP], Brett A Israels[SUP] 3 6 [/SUP], Aleksandra M Bednarz[SUP] 3 6 [/SUP], Claus Bus[SUP] 3 [/SUP], Benedikt Asbach[SUP] 7 [/SUP], David Peterhoff[SUP] 7 [/SUP], Finn S Pedersen[SUP] 4 [/SUP], Victoria Birkedal[SUP] 3 6 [/SUP], Ralf Wagner[SUP] 7 8 [/SUP], Søren R Paludan[SUP] 5 [/SUP], Jørgen Kjems[SUP] 1 2 4 [/SUP]
Affiliations
- PMID: 34876524
- DOI: 10.1073/pnas.2112942118
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 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.
Keywords: SARS-CoV-2 targeting; aptamer multimerization; aptamer selection; spike protein; viral neutralization.
