Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
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
_version_ 1784854874825949184
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
work_keys_str_mv AT yuchuandi screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT dingwen screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT zhulei screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT zhouyuhang screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT dongyingkui screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT liling screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT liujuanjuan screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT wangyizhuo screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT lizehua screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT zhulina screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT chenfajun screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT ruanmaosen screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT qiandongming screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT wangyujuan screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT wubo screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT xuhuangtao screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT liming screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT biyunchen screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT wanghao screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT wangweiqian screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT chaopeng screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT xinglei screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT shenbing screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT daihan screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT zhalisha screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT zhaohongxin screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins
AT wangjunfeng screeningandcharacterizationofinhibitoryvnartargetingnanodiscassembledinfluenzam2proteins