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Neutralizing Aptamers Block S/RBD‐ACE2 Interactions and Prevent Host Cell Infection
Author(s) -
Liu Xiaohui,
Wang Yiling,
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 Shuhsia,
Zu Youli
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202100345
Subject(s) - aptamer , virology , virus , receptor , coronavirus , viral entry , angiotensin converting enzyme 2 , oligonucleotide , biology , covid-19 , chemistry , microbiology and biotechnology , gene , infectious disease (medical specialty) , viral replication , biochemistry , disease , medicine , pathology
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 (IC 50 ≈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.