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

Xiaohui Liu, Yi ling Wang, Jacky Wu, Jianjun Qi, Zihua Zeng, Quanyuan Wan, Zhenghu Chen, Pragya Manandhar, Victoria S. Cavener, Nina R. Boyle, Xinping Fu, Eric Salazar, Suresh V. Kuchipudi, Vivek Kapur, Xiaoliu Zhang, Michihisa Umetani, Mehmet Sen, Richard C. Willson, Shu hsia Chen, Youli Zu

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)10273-10278
Number of pages6
JournalAngewandte Chemie - International Edition
Volume60
Issue number18
DOIs
StatePublished - Apr 26 2021

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)

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