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

Lujia Sun; Bianying Feng; Zezhong Liu; Jingqi Chen; Xiangwen Hao; Shuai Xia; Lu Lu; Qiuhong Man; Shibo Jiang; Xinling Wang

doi:10.1016/j.virs.2025.09.003

October 2025

Lujia Sun, Bianying Feng, Zezhong Liu, Jingqi Chen, Xiangwen Hao, Shuai Xia, Lu Lu, Qiuhong Man, Shibo Jiang and 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[J]. Virologica Sinica, 2025, 40(5): 856-859. doi: 10.1016/j.virs.2025.09.003

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

针对SARS-CoV-2 S2亚单位保守结构域的抗血清和抗病毒药物对具有溢出风险的使用ACE2作为受体的MERSr-CoVs感染有效

孙禄加 ^a ,
冯变莹 ^b ,
刘泽众 ^c ,
陈静奇 ^b ,
郝湘文 ^b ,
夏帅 ^a ,
陆路 ^a ,
满秋红 ^b,, ,
姜世勃 ^a,, ,
王欣玲 ^a,,

a 上海市重大传染病与生物安全研究院, 复旦大学基础医学院医学分子病毒学重点实验室, 上海, 200032;
b. 同济大学附属上海市第四人民医院检验科, 同济大学医学院, 上海, 200434;
c. 复旦大学药学院智能化递药教育部重点实验室, 上海, 201203

通讯作者： 满秋红, manqiuhong307@163.com; 姜世勃, shibojiang@fudan.edu.cn; 王欣玲, xinlingwang@fudan.edu.cn
收稿日期： 2025-06-28
录用日期： 2025-09-12

摘要

鉴于其多样性、广泛分布及传播能力，利用ACE2作为受体的MERS相关冠状病毒（MERSr-CoVs）的出现具有潜在溢出风险。本研究发现，BA.5/BF.7感染患者血清仅对部分MERSr-CoVs（如MOW15-22和BtHKU5-CoV-2）具有交叉中和，表明SARS-CoV-2感染个体血清对MERSr-CoVs的交叉反应有限。使用SARS-CoV-2 RBD免疫猕猴未能诱导产生MERSr-CoVs交叉中和抗体，但HR1LS（一种包含保守S2结构域HR1-CH-SH的亚单位疫苗）免疫后的小鼠血清对MERSr-CoV假病毒显示出较强的中和活性。上述结果表明发挥交叉中和作用的抗体很可能靶向保守的S2结构域。此外，HR1LS蛋白作为抑制剂，对上述MERSr-CoVs展现出广泛的抗病毒活性。研究结果表明，由感染诱导的抗体对以ACE2为受体的MERSr-CoVs的交叉反应有限，凸显出以S2为靶点的泛冠状病毒疫苗和抗病毒药物的研发在防控此类MERSr-CoVs溢出威胁的潜力。
- MERS相关冠状病毒(MERSr-CoVs)
- , 血管紧张素转化酶2(ACE2)
- , 康复者
- , 泛冠状病毒疫苗
- , S2亚基

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

Lujia Sun ^a ,
Bianying Feng ^b ,
Zezhong Liu ^c ,
Jingqi Chen ^b ,
Xiangwen Hao ^b ,
Shuai Xia ^a ,
Lu Lu ^a ,
Qiuhong Man ^b,, ,
Shibo Jiang ^a,, ,
Xinling Wang ^a,,

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

Corresponding author: Qiuhong Man, manqiuhong307@163.com Shibo Jiang, shibojiang@fudan.edu.cn Xinling Wang, xinlingwang@fudan.edu.cn
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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通讯作者: 陈斌, bchen63@163.com

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沈阳化工大学材料科学与工程学院沈阳 110142

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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针对SARS-CoV-2 S2亚单位保守结构域的抗血清和抗病毒药物对具有溢出风险的使用ACE2作为受体的MERSr-CoVs感染有效

摘要

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

Abstract

References

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Electronic Supplementary Material

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通讯作者: 陈斌, bchen63@163.com