Screening and characterization of inhibitory vNAR targeting nanodisc-assembled influenza M2 proteins
Summary: 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 environmen...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222020090 |
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| author | Chuandi Yu Wen Ding Lei Zhu Yuhang Zhou Yingkui Dong Ling Li Juanjuan Liu Yizhuo Wang Zehua Li Lina Zhu FaJun Chen Maosen Ruan Dongming Qian Yujuan Wang Bo Wu Huangtao Xu Ming Li Yunchen Bi Hao Wang Weiqian Wang Peng Chao Lei Xing Bing Shen Han Dai Lisha Zha Hongxin Zhao Junfeng Wang |
| author_facet | Chuandi Yu Wen Ding Lei Zhu Yuhang Zhou Yingkui Dong Ling Li Juanjuan Liu Yizhuo Wang Zehua Li Lina Zhu FaJun Chen Maosen Ruan Dongming Qian Yujuan Wang Bo Wu Huangtao Xu Ming Li Yunchen Bi Hao Wang Weiqian Wang Peng Chao Lei Xing Bing Shen Han Dai Lisha Zha Hongxin Zhao Junfeng Wang |
| author_sort | Chuandi Yu |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-04-10T21:06:09Z |
| format | Article |
| id | doaj.art-1a78a5e934174b078a443c01a3f376a5 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T21:06:09Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-1a78a5e934174b078a443c01a3f376a52023-01-22T04:40:38ZengElsevieriScience2589-00422023-01-01261105736Screening and characterization of inhibitory vNAR targeting nanodisc-assembled influenza M2 proteinsChuandi Yu0Wen Ding1Lei Zhu2Yuhang Zhou3Yingkui Dong4Ling Li5Juanjuan Liu6Yizhuo Wang7Zehua Li8Lina Zhu9FaJun Chen10Maosen Ruan11Dongming Qian12Yujuan Wang13Bo Wu14Huangtao Xu15Ming Li16Yunchen Bi17Hao Wang18Weiqian Wang19Peng Chao20Lei Xing21Bing Shen22Han Dai23Lisha Zha24Hongxin Zhao25Junfeng Wang26High Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China; University of Science and Technology of China, Hefei, Anhui 230026, ChinaSchool of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, ChinaHigh Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, ChinaInternational Immunology Centre, Anhui Agricultural University, Hefei, Anhui 230036, ChinaHigh Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China; Institute of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230039, ChinaHigh Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, ChinaHigh Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, ChinaHigh Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China; University of Science and Technology of China, Hefei, Anhui 230026, ChinaHigh Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China; University of Science and Technology of China, Hefei, Anhui 230026, ChinaHigh Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China; University of Science and Technology of China, Hefei, Anhui 230026, ChinaHigh Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China; School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, ChinaHigh Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, ChinaHefei China Science Longwood Biological Technology Co., Ltd. Hefei, Anhui 230088, ChinaHigh Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, ChinaHigh Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, ChinaHigh Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, ChinaHigh Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China; University of Science and Technology of China, Hefei, Anhui 230026, ChinaCAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for OceanMega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, Shandong 266071, China; Marine Biology and Biotechnology Laboratory, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, Shandong 266237, ChinaCAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for OceanMega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, Shandong 266071, China; Marine Biology and Biotechnology Laboratory, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, Shandong 266237, ChinaNational Facility for Protein Science in Shanghai, Shanghai Advanced Research Institute, Chinese Academy of Science, Shanghai 201210, ChinaNational Facility for Protein Science in Shanghai, Shanghai Advanced Research Institute, Chinese Academy of Science, Shanghai 201210, ChinaHigh Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China; University of Science and Technology of China, Hefei, Anhui 230026, ChinaSchool of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, ChinaHigh Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, ChinaInternational Immunology Centre, Anhui Agricultural University, Hefei, Anhui 230036, China; Corresponding authorHigh Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China; Hefei China Science Longwood Biological Technology Co., Ltd. Hefei, Anhui 230088, China; Corresponding authorHigh Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China; University of Science and Technology of China, Hefei, Anhui 230026, China; Institute of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230039, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004222020090VirologyNanoparticles |
| spellingShingle | Chuandi Yu Wen Ding Lei Zhu Yuhang Zhou Yingkui Dong Ling Li Juanjuan Liu Yizhuo Wang Zehua Li Lina Zhu FaJun Chen Maosen Ruan Dongming Qian Yujuan Wang Bo Wu Huangtao Xu Ming Li Yunchen Bi Hao Wang Weiqian Wang Peng Chao Lei Xing Bing Shen Han Dai Lisha Zha Hongxin Zhao Junfeng Wang Screening and characterization of inhibitory vNAR targeting nanodisc-assembled influenza M2 proteins iScience Virology Nanoparticles |
| 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 | Virology Nanoparticles |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222020090 |
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