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Volume 40 Issue 5
October 2025
    Citation: Lujia Sun, Bianying Feng, Zezhong Liu, Jingqi Chen, Xiangwen Hao, Shuai Xia, Lu Lu, Qiuhong Man, Shibo Jiang, Xinling Wang. Antisera and antivirals targeting the conserved domains in SARS-CoV-2 S2 subunit are effective against ACE2-using MERSr-CoVs with spillover potential .VIROLOGICA SINICA, 2025, 40(5) : 856-859.  http://dx.doi.org/10.1016/j.virs.2025.09.003
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    Antisera and antivirals targeting the conserved domains in SARS-CoV-2 S2 subunit are effective against ACE2-using MERSr-CoVs with spillover potential

    • a. Shanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology of MOE/NHC/CAMS, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China;

    • b. Department of Clinical Laboratory, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China;

    • c. Department of Pharmacology & Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, 201203, China

    • Highlights1. S2 subunit remains high conserved throughout coronavirus evolution.2. BA.5/BF.7-infection induces weak cross-immune response against MERS-related coronaviruses (MERSr-CoVs) in humans.3. HR1LS based on conserved S2 elicits strong cross-immune response to MERSr-CoVs in mice.4. Conserved domains in S2 represent ideal targets for pan-CoV vaccines and antivirals.
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      10.1016j.virs.2025.09.003-ESM1.docx

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      2. Jiang S, Wu F. 2025. Global surveillance and countermeasures for ACE2-using MERS-related coronaviruses with spillover risk. Cell, 188: 1465-1468.

      3. Liu Z, Zhou J, Wang W, Zhang G, Xing L, Zhang K, Wang Y, Xu W, Wang Q, Man Q, Wang Q, Ying T, Zhu Y, Jiang S, Lu L. 2024. Neutralization of SARS-CoV-2 BA.2.86 and JN.1 by CF501 adjuvant-enhanced immune responses targeting the conserved epitopes in ancestral RBD. Cell Rep. Med., 5: 101445.

      4. Liu Z, Zhou J, Xu W, Deng W, Wang Y, Wang M, Wang Q, Hsieh M, Dong J, Wang X, Huang W, Xing L, He M, Tao C, Xie Y, Zhang Y, Wang Y, Zhao J, Yuan Z, Qin C, Jiang S, Lu L. 2022. A novel STING agonist-adjuvanted pan-sarbecovirus vaccine elicits potent and durable neutralizing antibody and T cell responses in mice, rabbits and NHPs. Cell Res., 32: 269-287.

      5. Lu L, Su S, Yang H, Jiang S. 2021. Antivirals with common targets against highly pathogenic viruses. Cell, 184: 1604-1620.

      6. Ma CB, Liu C, Park YJ, Tang J, Chen J, Xiong Q, Lee J, Stewart C, Asarnow D, Brown J, Tortorici MA, Yang X, Sun YH, Chen YM, Yu X, Si JY, Liu P, Tong F, Huang ML, Li J, Shi ZL, Deng Z, Veesler D, Yan H. 2025. Multiple independent acquisitions of ACE2 usage in MERS-related coronaviruses. Cell, 188: 1693-1710 e1618.

      7. Meyerholz DK, Lambertz AM, McCray PB, Jr. 2016. Dipeptidyl peptidase 4 distribution in the human respiratory tract: implications for the Middle East respiratory syndrome. Am. J. Pathol., 186: 78-86.

      8. Park YJ, Liu C, Lee J, Brown JT, Ma CB, Liu P, Gen R, Xiong Q, Zepeda SK, Stewart C, Addetia A, Craig CJ, Tortorici MA, Alshukairi AN, Starr TN, Yan H, Veesler D. 2025. Molecular basis of convergent evolution of ACE2 receptor utilization among HKU5 coronaviruses. Cell, 188: 1711-1728 e1721.

      9. Peng Y, Liu Y, Hu Y, Chang F, Wu Q, Yang J, Chen J, Teng S, Zhang J, He R, Wei Y, Bostina M, Luo T, Liu W, Qu X, Li YP. 2022. Monoclonal antibodies constructed from COVID-19 convalescent memory B cells exhibit potent binding activity to MERS-CoV spike S2 subunit and other human coronaviruses. Front. Immunol., 13: 1056272.

      10. Sun L, Man Q, Zhang H, Xia S, Lu L, Wang X, Xiong L, Jiang S. 2024. Strong cross immune responses against sarbecoviruses but not merbecoviruses in SARS-CoV-2 BA.5/BF.7-infected individuals with or without inactivated COVID-19 vaccination. J. Infect., 88: 106138.

      11. Sun S, He J, Liu L, Zhu Y, Zhang Q, Qiu Y, Han Y, Xue S, Peng X, Long Y, Lu T, Wu W, Xia A, Zhou Y, Yan Y, Gao Y, Lu L, Sun L, Xie M, Wang Q. 2025. Anti-S2 antibodies responsible for the SARS-CoV-2 infection-induced serological cross-reactivity against MERS-CoV and MERS-related coronaviruses. Front. Immunol., 16: 1541269.

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      13. Wang X, Sun L, Liu Z, Xing L, Zhu Y, Xu W, Xia S, Lu L, Jiang S. 2023. An engineered recombinant protein containing three structural domains in SARS-CoV-2 S2 protein has potential to act as a pan-human coronavirus entry inhibitor or vaccine antigen. Emerg. Microb. Infect., 12: 2244084.

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      Antisera and antivirals targeting the conserved domains in SARS-CoV-2 S2 subunit are effective against ACE2-using MERSr-CoVs with spillover potential

        Corresponding author: Qiuhong Man, manqiuhong307@163.com
        Corresponding author: Shibo Jiang, shibojiang@fudan.edu.cn
        Corresponding author: Xinling Wang, xinlingwang@fudan.edu.cn
      • a. Shanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology of MOE/NHC/CAMS, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China;
      • b. Department of Clinical Laboratory, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China;
      • c. Department of Pharmacology & Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, 201203, China
      • Received Date: 28 June 2025
      • Accepted Date: 12 September 2025

      Abstract: Highlights1. S2 subunit remains high conserved throughout coronavirus evolution.2. BA.5/BF.7-infection induces weak cross-immune response against MERS-related coronaviruses (MERSr-CoVs) in humans.3. HR1LS based on conserved S2 elicits strong cross-immune response to MERSr-CoVs in mice.4. Conserved domains in S2 represent ideal targets for pan-CoV vaccines and antivirals.

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