. doi: 10.1016/j.virs.2022.07.001
Citation: Mengyuan Chen, Shuizhen He, Hualong Xiong, Dongxu Zhang, Shaojuan Wang, Wangheng Hou, Xiaomei Zhu, Jin Wang, Yang Huang, Congming Hong, Yubin Wu, Ruoyao Qi, Tianying Zhang, Quan Yuan, Tingdong Li, Yixin Chen, Shiyin Zhang, Shengxiang Ge, Jun Zhang, Ningshao Xia. New discovery of high-affinity SARS-CoV-2 spike S2 protein binding peptide selected by PhIP-Seq .VIROLOGICA SINICA, 2022, 37(5) : 758-761.  http://dx.doi.org/10.1016/j.virs.2022.07.001

基于PhIP-Seq技术新筛选出SARS-CoV-2 spike蛋白S2亚基的高亲和力结合短肽

  • SARS-CoV-2感染引起的COVID-19带来了全球性的威胁,靶向SARS-CoV-2 S蛋白的预防与治疗将是控制COVID-19的有效手段。而高亲和力的结合分子是靶向研究的重要基础。本研究利用PhIP-Seq技术筛选出了靶向SARS-CoV-2 S蛋白的结合多肽Spep-1。经鉴定,该肽靶向结合S蛋白的S2亚基,其与S蛋白具有高亲和力和高特异性,Spep-1/S三聚体复合物的Kd值为1.7 nmol/L,Spep-1/S单体复合物的Kd值为2.14 nmol/L。本研究初步将其应用于血清中S蛋白的检测,基于Spep-1建立的ELISA方法,可以检测出血清中低至飞摩尔级别的S蛋白。本研究新鉴定出的结合多肽Spep-1,在未来的研究中经过理性修饰,将促进病毒入胞、体内病毒示踪、药物靶向递送等研究。

New discovery of high-affinity SARS-CoV-2 spike S2 protein binding peptide selected by PhIP-Seq

  • Highlights
    1 A peptide Spep-1 targeting S2 of SARS-CoV-2 spike protein was selected by PhIP-Seq.
    2 Spep-1 showed nanomolar affinity and high specificity to spike protein.
    3 S-1 based immunoassay can detect femtomolar spike antigen in spiked serum samples.
    4 Spep-1 can be used in future on S2 recognition, virus tracing and drug delivery.

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    1. Case, J.B., Chen, R.E., Cao, L., Ying, B., Winkler, E.S., Johnson, M., Goreshnik, I., Pham, M.N., Shrihari, S., Kafai, N.M., Bailey, A.L., Xie, X., Shi, P.Y., Ravichandran, R., Carter, L., Stewart, L., Baker, D., Diamond, M.S., 2021. Ultrapotent miniproteins targeting the receptor-binding domain protect against SARS-CoV-2 infection and disease in mice. Cell Host Microbe 29, 1151-1161.e5.

    2. Gavor, E., Choong, Y., Er, S., Sivaraman, H., Sivaraman, J., 2020. Structural basis of SARSCoV-2 and SARS-CoV antibody interactions. Trends Immunol. 41, 1006-1022.

    3. Hao, J., Wang, F., Xing, G., Liu, Y., Deng, R., Zhang, H., Cheng, A., Zhang, G., 2019. Design and preliminary application of affinity peptide based on the structure of the porcine circovirus type II capsid (PCV2 cap). PeerJ 7, e8132.

    4. Harvey, W., Carabelli, A., Jackson, B., Gupta, R., Thomson, E., Harrison, E., Ludden, C., Reeve, R., Rambaut, R.,, COVID-19 Genomics UK (COG-UK) Consortium, Peacock, S., Robertson, D., 2021. SARS-CoV-2 variants, spike mutations and immune escape. Nat. Rev. Microbiol. 19, 409-424.

    5. Mendoza-Figueroa, J., Kvarnheden, A., Méndez-Lozano, J., Rodríguez-Negrete, E., Monteros, R., Soriano-García, M., 2018. A peptide derived from enzymatic digestion of globulins from amaranth shows strong affinity binding to the replication origin of tomato yellow leaf curl virus reducing viral replication in nicotiana benthamiana. Pestic. Biochem. Physiol. 145, 56-65.

    6. Ng, K., Mohd-Ismail, N., Tan, Y., 2021. Spike S2 subunit:the dark horse in the race for prophylactic and therapeutic interventions against SARS-CoV-2. Vaccines (Basel) 9, 178.

    7. Norman, A., Franck, C., Christie, M., Hawkins, H., Patel, K., Ashhurst, A., Aggarwal, A., Low, J., Siddiquee, R., Ashley, C., Steain, M., Triccas, J., Turville, S., Mackay, J., Passioura, T., Payne, R., 2021. Discovery of cyclic peptide ligands to the SARS-CoV-2 spike protein using mrna display. ACS Cent. Sci. 7, 1001-1008.

    8. Pei, P., Qin, H., Chen, J., Wang, F., He, C., He, S., Hong, B., Liu, K., Qiao, R., Fan, H., Tong, Y., Chen, L., Luo, S., 2021. Computational design of ultrashort peptide inhibitors of the receptor-binding domain of the SARS-CoV-2 S protein. Briefings Bioinf. 22, bbab243.

    9. Pomplun, S., Jbara, M., Quartararo, A., Zhang, G., Brown, J., Lee, Y., Ye, X., Hanna, S., Pentelute, B., 2021. De novo discovery of high-affinity peptide binders for the SARSCoV-2 spike protein. ACS Cent. Sci. 7, 156-163.

    10. Rosestedt, M., Velikyan, I., Rosenström, U., Estrada, S., Åberg, O., Weis, J., Westerlund, C., Ingvast, S., Korsgren, O., Nordeman, P., Eriksson, O., 2021. Radiolabelling and positron emission tomography imaging of a high-affinity peptide binder to collagen type 1. Nucl. Med. Biol. 93, 54-62.

    11. Singhal, S., Khanna, P., Khanna, L., 2021. Synthesis, comparative in vitro antibacterial, antioxidant and UV fluorescence studies of bis indole schiff bases and molecular docking with ct-DNA and SARS-CoV-2 Mpro. Luminescence 36, 1531-1543.

    12. Ucar, B., Acar, T., Arayici, P., Derman, S., 2021. A nanotechnological approach in the current therapy of COVID-19:model drug oseltamivir-phosphate loaded PLGA nanoparticles targeted with spike protein binder peptide of SARS-CoV-2.Nanotechnology. https://doi.org/10.1088/1361-6528/ac1c22.

    13. Xiong, H., Wu, Y., Cao, J., Yang, R., Liu, Y., Ma, J., Qiao, X., Yao, X., Zhang, B., Zhang, Y., Hou, W., Shi, Y., Xu, J., Zhang, L., Wang, S., Fu, B., Yang, T., Ge, S., Zhang, J., Yuan, Q., Huang, B., Li, Z., Zhang, T., Xia, N., 2020. Robust neutralization assay based on SARS-CoV-2 S-protein-bearing vesicular stomatitis virus (VSV) pseudovirus and ACE2-overexpressing BHK21 cells. Emerg. Microb. Infect. 9, 2105-2113.

    14. Zhao, H., To, K., Sze, K., Yung, T., Bian, M., Lam, H., Yeung, M., Li, C., Chu, H., Yuen, K., 2020. A broad-spectrum virus- and host-targeting peptide against respiratory viruses including influenza virus and SARS-CoV-2. Nat. Commun. 11, 4252.

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    New discovery of high-affinity SARS-CoV-2 spike S2 protein binding peptide selected by PhIP-Seq

      Corresponding author: Shiyin Zhang, zhangshiyin@xmu.edu.cn
      Corresponding author: Shengxiang Ge, sxge@xmu.edu.cn
    • a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, South Xiang'an Road, Xiamen, 361102, China;
    • b Xiamen Haicang Hospital, Haiyu Road, Xiamen, 361026, China;
    • c School of Life Sciences, Xiamen University, South Xiang'an Road, Xiamen, 361102, China

    Abstract: Highlights
    1 A peptide Spep-1 targeting S2 of SARS-CoV-2 spike protein was selected by PhIP-Seq.
    2 Spep-1 showed nanomolar affinity and high specificity to spike protein.
    3 S-1 based immunoassay can detect femtomolar spike antigen in spiked serum samples.
    4 Spep-1 can be used in future on S2 recognition, virus tracing and drug delivery.

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