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

doi:10.1002/anie.202100345

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 journal › Article › peer-review

113 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 (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.

Original language	English (US)
Pages (from-to)	10273-10278
Number of pages	6
Journal	Angewandte Chemie - International Edition
Volume	60
Issue number	18
DOIs	https://doi.org/10.1002/anie.202100345
State	Published - Apr 26 2021

Keywords

COVID-19
SARS-CoV-2
aptamers
receptor-binding domain (RBD)
virus neutralization
COVID-19/drug therapy
Antiviral Agents/chemistry
Humans
Angiotensin-Converting Enzyme 2/metabolism
Spike Glycoprotein, Coronavirus/chemistry
SARS-CoV-2/chemistry
Protein Interaction Maps/drug effects
Base Sequence
HEK293 Cells
Aptamers, Nucleotide/chemistry
Protein Interaction Domains and Motifs/drug effects

ASJC Scopus subject areas

General Chemistry
Catalysis

Divisions

Medical Oncology

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10.1002/anie.202100345

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Liu, X., Wang, Y. L., Wu, J., Qi, J., Zeng, Z., Wan, Q., Chen, Z., Manandhar, P., Cavener, V. S., Boyle, N. R., Fu, X., Salazar, E., Kuchipudi, S. V., Kapur, V., Zhang, X., Umetani, M., Sen, M., Willson, R. C., Chen, S. H., & Zu, Y. (2021). Neutralizing Aptamers Block S/RBD-ACE2 Interactions and Prevent Host Cell Infection. Angewandte Chemie - International Edition, 60(18), 10273-10278. https://doi.org/10.1002/anie.202100345

Liu, X, Wang, YL, Wu, J, Qi, J, Zeng, Z, Wan, Q, Chen, Z, Manandhar, P, Cavener, VS, Boyle, NR, Fu, X, Salazar, E, Kuchipudi, SV, Kapur, V, Zhang, X, Umetani, M, Sen, M, Willson, RC , Chen, SH & Zu, Y 2021, 'Neutralizing Aptamers Block S/RBD-ACE2 Interactions and Prevent Host Cell Infection', Angewandte Chemie - International Edition, vol. 60, no. 18, pp. 10273-10278. https://doi.org/10.1002/anie.202100345

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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.",

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

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AU - Liu, Xiaohui

AU - Wang, Yi ling

AU - Wu, Jacky

AU - Qi, Jianjun

AU - Zeng, Zihua

AU - Wan, Quanyuan

AU - Chen, Zhenghu

AU - Manandhar, Pragya

AU - Cavener, Victoria S.

AU - Boyle, Nina R.

AU - Fu, Xinping

AU - Salazar, Eric

AU - Kuchipudi, Suresh V.

AU - Kapur, Vivek

AU - Zhang, Xiaoliu

AU - Umetani, Michihisa

AU - Sen, Mehmet

AU - Willson, Richard C.

AU - Chen, Shu hsia

AU - Zu, Youli

PY - 2021/4/26

Y1 - 2021/4/26

N2 - 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.

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KW - Protein Interaction Maps/drug effects

KW - Base Sequence

KW - HEK293 Cells

KW - Aptamers, Nucleotide/chemistry

KW - Protein Interaction Domains and Motifs/drug effects

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

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