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

Area of Science:

• Molecular biology
• Virology
• Biotechnology

Background:

• The SARS-CoV-2 spike protein's receptor-binding domain (RBD) is crucial for viral entry by binding to human ACE2 receptors.
• Targeting the S/RBD is a key strategy for developing therapies against COVID-19.

Purpose of the Study:

• To develop novel oligonucleotide aptamers that specifically target the SARS-CoV-2 S/RBD.
• To evaluate the efficacy of these aptamers in blocking S/RBD interaction with ACE2 and neutralizing viral particles.

Main Methods:

• Utilized a target-based selection approach to design and synthesize oligonucleotide aptamers.
• Assessed aptamer binding affinity to S/RBD using surface plasmon resonance (SPR) or similar techniques.
• Measured the inhibition of S/RBD and ACE2 interaction and viral neutralization capabilities of the aptamers.

Main Results:

• Developed synthetic aptamers with high binding affinity for S/RBD (K_D ≈ 7 nM).
• Demonstrated that aptamers effectively blocked S/RBD binding to ACE2 receptors (IC₅₀ ≈ 5 nM).
• Showed aptamer-mediated neutralization of S protein-expressing viral particles, preventing host cell infection.

Conclusions:

• Oligonucleotide aptamers targeting the SARS-CoV-2 S/RBD are effective inhibitors of viral binding and entry.
• These aptamers represent a promising therapeutic strategy for preventing and treating COVID-19.