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

81 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

Chemistry(all)
Catalysis

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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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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

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

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