tetano
Editor, Senior Moderator
iScience
. 2022 Dec 5;26(1):105736.
doi: 10.1016/j.isci.2022.105736. eCollection 2023 Jan 20.
Screening and characterization of inhibitory vNAR targeting nanodisc-assembled influenza M2 proteins
Chuandi Yu[SUP] 1 2 [/SUP], Wen Ding[SUP] 3 [/SUP], Lei Zhu[SUP] 1 [/SUP], Yuhang Zhou[SUP] 4 [/SUP], Yingkui Dong[SUP] 1 5 [/SUP], Ling Li[SUP] 1 [/SUP], Juanjuan Liu[SUP] 1 [/SUP], Yizhuo Wang[SUP] 1 2 [/SUP], Zehua Li[SUP] 1 2 [/SUP], Lina Zhu[SUP] 1 2 [/SUP], FaJun Chen[SUP] 1 3 [/SUP], Maosen Ruan[SUP] 1 [/SUP], Dongming Qian[SUP] 6 [/SUP], Yujuan Wang[SUP] 1 [/SUP], Bo Wu[SUP] 1 [/SUP], Huangtao Xu[SUP] 1 [/SUP], Ming Li[SUP] 1 2 [/SUP], Yunchen Bi[SUP] 7 8 [/SUP], Hao Wang[SUP] 7 8 [/SUP], Weiqian Wang[SUP] 9 [/SUP], Peng Chao[SUP] 9 [/SUP], Lei Xing[SUP] 1 2 [/SUP], Bing Shen[SUP] 3 [/SUP], Han Dai[SUP] 1 [/SUP], Lisha Zha[SUP] 4 [/SUP], Hongxin Zhao[SUP] 1 6 [/SUP], Junfeng Wang[SUP] 1 2 5 [/SUP]
Affiliations
Abstract
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.
Keywords: Nanoparticles; Virology.
. 2022 Dec 5;26(1):105736.
doi: 10.1016/j.isci.2022.105736. eCollection 2023 Jan 20.
Screening and characterization of inhibitory vNAR targeting nanodisc-assembled influenza M2 proteins
Chuandi Yu[SUP] 1 2 [/SUP], Wen Ding[SUP] 3 [/SUP], Lei Zhu[SUP] 1 [/SUP], Yuhang Zhou[SUP] 4 [/SUP], Yingkui Dong[SUP] 1 5 [/SUP], Ling Li[SUP] 1 [/SUP], Juanjuan Liu[SUP] 1 [/SUP], Yizhuo Wang[SUP] 1 2 [/SUP], Zehua Li[SUP] 1 2 [/SUP], Lina Zhu[SUP] 1 2 [/SUP], FaJun Chen[SUP] 1 3 [/SUP], Maosen Ruan[SUP] 1 [/SUP], Dongming Qian[SUP] 6 [/SUP], Yujuan Wang[SUP] 1 [/SUP], Bo Wu[SUP] 1 [/SUP], Huangtao Xu[SUP] 1 [/SUP], Ming Li[SUP] 1 2 [/SUP], Yunchen Bi[SUP] 7 8 [/SUP], Hao Wang[SUP] 7 8 [/SUP], Weiqian Wang[SUP] 9 [/SUP], Peng Chao[SUP] 9 [/SUP], Lei Xing[SUP] 1 2 [/SUP], Bing Shen[SUP] 3 [/SUP], Han Dai[SUP] 1 [/SUP], Lisha Zha[SUP] 4 [/SUP], Hongxin Zhao[SUP] 1 6 [/SUP], Junfeng Wang[SUP] 1 2 5 [/SUP]
Affiliations
- PMID: 36570769
- PMCID: PMC9771723
- DOI: 10.1016/j.isci.2022.105736
Abstract
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.
Keywords: Nanoparticles; Virology.