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
{"title":"中和Aptamers能阻断S/RBD-ACE2相互作用并防止宿主细胞感染","authors":"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/ange.202100345","DOIUrl":null,"url":null,"abstract":"<p><p>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 (<i>K</i> <sub>D</sub>≈7 nM) and also blocked interaction of S/RBD with ACE2 receptors (IC<sub>50</sub>≈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.</p>","PeriodicalId":72198,"journal":{"name":"Angewandte Chemie (Weinheim an der Bergstrasse, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2021-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250357/pdf/ANGE-133-10361.pdf","citationCount":"0","resultStr":"{\"title\":\"Neutralizing Aptamers Block S/RBD-ACE2 Interactions and Prevent Host Cell Infection.\",\"authors\":\"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/ange.202100345\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 (<i>K</i> <sub>D</sub>≈7 nM) and also blocked interaction of S/RBD with ACE2 receptors (IC<sub>50</sub>≈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.</p>\",\"PeriodicalId\":72198,\"journal\":{\"name\":\"Angewandte Chemie (Weinheim an der Bergstrasse, Germany)\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2021-04-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250357/pdf/ANGE-133-10361.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Angewandte Chemie (Weinheim an der Bergstrasse, Germany)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1002/ange.202100345\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2021/3/22 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Angewandte Chemie (Weinheim an der Bergstrasse, Germany)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/ange.202100345","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/3/22 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
Neutralizing Aptamers Block S/RBD-ACE2 Interactions and Prevent Host Cell Infection.
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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