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Screening and characterization of inhibitory vNAR targeting nanodisc-assembled influenza M2 proteins
Influenza A virus poses a constant challenge to human health. The highly conserved influenza matrix-2 (M2) protein is an attractive target for the development of a universal antibody-based drug. However, screening using antigens with subphysiological conformation in a nonmembrane environment signifi...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9771723/ https://www.ncbi.nlm.nih.gov/pubmed/36570769 http://dx.doi.org/10.1016/j.isci.2022.105736 |
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author | Yu, Chuandi Ding, Wen Zhu, Lei Zhou, Yuhang Dong, Yingkui Li, Ling Liu, Juanjuan Wang, Yizhuo Li, Zehua Zhu, Lina Chen, FaJun Ruan, Maosen Qian, Dongming Wang, Yujuan Wu, Bo Xu, Huangtao Li, Ming Bi, Yunchen Wang, Hao Wang, Weiqian Chao, Peng Xing, Lei Shen, Bing Dai, Han Zha, Lisha Zhao, Hongxin Wang, Junfeng |
author_facet | Yu, Chuandi Ding, Wen Zhu, Lei Zhou, Yuhang Dong, Yingkui Li, Ling Liu, Juanjuan Wang, Yizhuo Li, Zehua Zhu, Lina Chen, FaJun Ruan, Maosen Qian, Dongming Wang, Yujuan Wu, Bo Xu, Huangtao Li, Ming Bi, Yunchen Wang, Hao Wang, Weiqian Chao, Peng Xing, Lei Shen, Bing Dai, Han Zha, Lisha Zhao, Hongxin Wang, Junfeng |
author_sort | Yu, Chuandi |
collection | PubMed |
description | Influenza A virus poses a constant challenge to human health. The highly conserved influenza matrix-2 (M2) protein is an attractive target for the development of a universal antibody-based drug. However, screening using antigens with subphysiological conformation in a nonmembrane environment significantly reduces the generation of efficient antibodies. Here, M2(1-46) was incorporated into nanodiscs (M2-nanodiscs) with M2 in a membrane-embedded tetrameric conformation, closely resembling its natural physiological state in the influenza viral envelope. M2-nanodisc generation, an antigen, was followed by Chiloscyllium plagiosum immunization. The functional vNARs were selected by phage display panning strategy from the shark immune library. One of the isolated vNARs, AM2H10, could specifically bind to tetrameric M2 instead of monomeric M2e (the ectodomain of M2 protein). Furthermore, AM2H10 blocked ion influx through amantadine-sensitive and resistant M2 channels. Our findings indicated the possibility of developing functional shark nanobodies against various influenza viruses by targeting the M2 protein. |
format | Online Article Text |
id | pubmed-9771723 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-97717232022-12-23 Screening and characterization of inhibitory vNAR targeting nanodisc-assembled influenza M2 proteins Yu, Chuandi Ding, Wen Zhu, Lei Zhou, Yuhang Dong, Yingkui Li, Ling Liu, Juanjuan Wang, Yizhuo Li, Zehua Zhu, Lina Chen, FaJun Ruan, Maosen Qian, Dongming Wang, Yujuan Wu, Bo Xu, Huangtao Li, Ming Bi, Yunchen Wang, Hao Wang, Weiqian Chao, Peng Xing, Lei Shen, Bing Dai, Han Zha, Lisha Zhao, Hongxin Wang, Junfeng iScience Article Influenza A virus poses a constant challenge to human health. The highly conserved influenza matrix-2 (M2) protein is an attractive target for the development of a universal antibody-based drug. However, screening using antigens with subphysiological conformation in a nonmembrane environment significantly reduces the generation of efficient antibodies. Here, M2(1-46) was incorporated into nanodiscs (M2-nanodiscs) with M2 in a membrane-embedded tetrameric conformation, closely resembling its natural physiological state in the influenza viral envelope. M2-nanodisc generation, an antigen, was followed by Chiloscyllium plagiosum immunization. The functional vNARs were selected by phage display panning strategy from the shark immune library. One of the isolated vNARs, AM2H10, could specifically bind to tetrameric M2 instead of monomeric M2e (the ectodomain of M2 protein). Furthermore, AM2H10 blocked ion influx through amantadine-sensitive and resistant M2 channels. Our findings indicated the possibility of developing functional shark nanobodies against various influenza viruses by targeting the M2 protein. Elsevier 2022-12-05 /pmc/articles/PMC9771723/ /pubmed/36570769 http://dx.doi.org/10.1016/j.isci.2022.105736 Text en © 2022. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Yu, Chuandi Ding, Wen Zhu, Lei Zhou, Yuhang Dong, Yingkui Li, Ling Liu, Juanjuan Wang, Yizhuo Li, Zehua Zhu, Lina Chen, FaJun Ruan, Maosen Qian, Dongming Wang, Yujuan Wu, Bo Xu, Huangtao Li, Ming Bi, Yunchen Wang, Hao Wang, Weiqian Chao, Peng Xing, Lei Shen, Bing Dai, Han Zha, Lisha Zhao, Hongxin Wang, Junfeng Screening and characterization of inhibitory vNAR targeting nanodisc-assembled influenza M2 proteins |
title | Screening and characterization of inhibitory vNAR targeting nanodisc-assembled influenza M2 proteins |
title_full | Screening and characterization of inhibitory vNAR targeting nanodisc-assembled influenza M2 proteins |
title_fullStr | Screening and characterization of inhibitory vNAR targeting nanodisc-assembled influenza M2 proteins |
title_full_unstemmed | Screening and characterization of inhibitory vNAR targeting nanodisc-assembled influenza M2 proteins |
title_short | Screening and characterization of inhibitory vNAR targeting nanodisc-assembled influenza M2 proteins |
title_sort | screening and characterization of inhibitory vnar targeting nanodisc-assembled influenza m2 proteins |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9771723/ https://www.ncbi.nlm.nih.gov/pubmed/36570769 http://dx.doi.org/10.1016/j.isci.2022.105736 |
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