Neutralizing Aptamers Block S/RBD-ACE2 Interactions and Prevent Host Cell Infection.
Xiaohui LiuYi-Ling WangJacky WuJianjun QiZihua ZengQuanyuan WanZhenghu ChenPragya ManandharVictoria S CavenerNina R BoyleXinping FuEric SalazarSuresh V KuchipudiVivek KapurXiaoliu ZhangMichihisa UmetaniMehmet SenRichard C WillsonShu-Hsia ChenYouli ZuPublished in: Angewandte Chemie (Weinheim an der Bergstrasse, Germany) (2021)
The receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 spike (S) protein plays a central role in mediating the first step of virus infection to cause disease: virus binding to angiotensin-converting enzyme 2 (ACE2) receptors on human host cells. Therefore, S/RBD is an ideal target for blocking and neutralization therapies to prevent and treat coronavirus disease 2019 (COVID-19). Using a target-based selection approach, we developed oligonucleotide aptamers containing a conserved sequence motif that specifically targets S/RBD. Synthetic aptamers had high binding affinity for S/RBD-coated virus mimics (K D≈7 nM) and also blocked interaction of S/RBD with ACE2 receptors (IC50≈5 nM). Importantly, aptamers were able to neutralize S protein-expressing viral particles and prevent host cell infection, suggesting a promising COVID-19 therapy strategy.
Keyphrases
- coronavirus disease
- angiotensin converting enzyme
- respiratory syndrome coronavirus
- sars cov
- angiotensin ii
- binding protein
- disease virus
- nucleic acid
- cell therapy
- single cell
- photodynamic therapy
- induced apoptosis
- endothelial cells
- protein protein
- transcription factor
- amino acid
- dna binding
- mesenchymal stem cells
- cell cycle arrest
- stem cells
- endoplasmic reticulum stress
- zika virus
- smoking cessation
- wild type
- dengue virus