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- Title
Neutralizing Aptamers Block S/RBD‐ACE2 Interactions and Prevent Host Cell Infection.
- Authors
Liu, Xiaohui; Wang, Yi‐ling; Wu, Jacky; Qi, Jianjun; Zeng, Zihua; Wan, Quanyuan; Chen, Zhenghu; Manandhar, Pragya; Cavener, Victoria S.; Boyle, Nina R.; Fu, Xinping; Salazar, Eric; Kuchipudi, Suresh V.; Kapur, Vivek; Zhang, Xiaoliu; Umetani, Michihisa; Sen, Mehmet; Willson, Richard C.; Chen, Shu‐hsia; Zu, Youli
- Abstract
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 (KD≈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.
- Subjects
COVID-19; COVID-19 treatment; VIRUS diseases; ANGIOTENSIN converting enzyme
- Publication
Angewandte Chemie, 2021, Vol 133, Issue 18, p10361
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.202100345