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Neutralizing Aptamers Block S/RBD-ACE2 Interactions and Prevent Host Cell Infection
Xiaohui Liu1, Yi-Ling Wang2, Jacky Wu3
1Department of Pathology and Genomic Medicine Houston Methodist Hospital Houston TX 77030 USA.
Summary
Researchers developed aptamers targeting the SARS-CoV-2 spike protein's receptor-binding domain (RBD). These aptamers effectively block viral entry into host cells, showing promise as a COVID-19 therapy.
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 (KD ≈ 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.

