Neutralizing Aptamers Block S/RBD-ACE2 Interactions and Prevent Host Cell Infection

Area of Science:

• Virology
• Molecular Biology
• Drug Discovery

Background:

• The SARS-CoV-2 spike protein's receptor-binding domain (RBD) is crucial for viral entry into host cells by binding to ACE2 receptors.
• This interaction is a primary target for developing therapies against COVID-19.

Purpose of the Study:

• To develop novel oligonucleotide aptamers that specifically target the SARS-CoV-2 spike protein's RBD.
• To evaluate the efficacy of these aptamers in blocking viral entry and neutralizing SARS-CoV-2.

Main Methods:

• A target-based selection approach was employed to design and synthesize specific oligonucleotide aptamers.
• Binding affinity and inhibitory concentrations (IC50) were determined using S/RBD-coated virus mimics and ACE2 receptor interaction assays.
• Neutralization assays were performed using S protein-expressing viral particles to assess efficacy in preventing host cell infection.

Main Results:

• Developed synthetic aptamers demonstrated high binding affinity for S/RBD (KD ≈7 nM).
• The aptamers effectively blocked the interaction between S/RBD and ACE2 receptors (IC50 ≈5 nM).
• Aptamers successfully neutralized S protein-expressing viral particles, preventing host cell infection.

Conclusions:

• Oligonucleotide aptamers targeting the SARS-CoV-2 S/RBD represent a promising therapeutic strategy for COVID-19.
• These aptamers show potential for blocking viral entry and neutralizing infectious viral particles.