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

Area of Science:

• Biotechnology
• Molecular Biology
• Virology

Background:

• The COVID-19 pandemic necessitates innovative therapeutic strategies against SARS-CoV-2.
• The SARS-CoV-2 spike protein's receptor binding domain (RBD) is crucial for viral entry via ACE2 interaction.

Purpose of the Study:

• To develop a high-affinity RNA aptamer targeting the SARS-CoV-2 spike protein RBD.
• To evaluate the aptamer's potential for blocking viral infection and its applicability to emerging variants.

Main Methods:

• Design and synthesis of a 2'-fluoro protected RNA aptamer.
• Affinity and specificity assessment using biolayer interferometry, single-molecule fluorescence microscopy, and flow-induced dispersion analysis.
• In vitro evaluation of antiviral activity using virus-like particles and live SARS-CoV-2.

Main Results:

• The RNA aptamer exhibits high-affinity binding to the SARS-CoV-2 spike protein RBD.
• A trimerized aptamer version significantly enhances binding affinity to the picomolar range.
• Both aptamer forms efficiently inhibit viral infection in cell culture at low concentrations.
• The aptamer retains high affinity for spike proteins from various SARS-CoV-2 strains.

Conclusions:

• A potent RNA aptamer targeting the SARS-CoV-2 spike protein RBD has been developed.
• The aptamer demonstrates significant antiviral activity and potential for broad application against SARS-CoV-2 and its variants.
• This RNA aptamer offers a promising avenue for COVID-19 detection and treatment.