Identification of an immunogenic epitope and protective antibody against the furin cleavage site of SARS-CoV-2

Lili Li, Meiling Gao, Jie Li, Xuping Xie, Hui Zhao, Yanan Wang, Xin Xu, Shulong Zu, Chunfeng Chen, Dingyi Wan, Jing Duan, Jingfeng Wang, Saba R. Aliyari, Sarah Gold, Jicai Zhang, Cheng Feng Qin, Pei Yong Shi, Heng Yang, Genhong Cheng

Research output: Contribution to journalArticlepeer-review


Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the global coronavirus disease 2019 (COVID-19) pandemic, contains a unique, four amino acid (aa) “PRRA” insertion in the spike (S) protein that creates a transmembrane protease serine 2 (TMPRSS2)/furin cleavage site and enhances viral infectivity. More research into immunogenic epitopes and protective antibodies against this SARS-CoV-2 furin cleavage site is needed. Methods: Combining computational and experimental methods, we identified and characterized an immunogenic epitope overlapping the furin cleavage site that detects antibodies in COVID-19 patients and elicits strong antibody responses in immunized mice. We also identified a high-affinity monoclonal antibody from COVID-19 patient peripheral blood mononuclear cells; the antibody directly binds the furin cleavage site and protects against SARS-CoV-2 infection in a mouse model. Findings: The presence of “PRRA” amino acids in the S protein of SARS-CoV-2 not only creates a furin cleavage site but also generates an immunogenic epitope that elicits an antibody response in COVID-19 patients. An antibody against this epitope protected against SARS-CoV-2 infection in mice. Interpretation: The immunogenic epitope and protective antibody we have identified may augment our strategy in handling COVID-19 epidemic. Funding: The National Natural Science Foundation of China ( 82102371, 91542201, 81925025, 82073181, and 81802870), the Chinese Academy of Medical Sciences Initiative for Innovative Medicine ( 2021-I2M-1-047 and 2022-I2M-2-004), the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences ( 2020-PT310-006, 2019XK310002, and 2018TX31001), the National Key Research and Development Project of China ( 2020YFC0841700), US National Institute of Health (NIH) funds grant AI158154, University of California Los Angeles (UCLA) AI and Charity Treks, and UCLA DGSOM BSCRC COVID-19 Award Program. H.Y. is supported by Natural Science Foundation of Jiangsu Province ( BK20211554 and BE2022728).

Original languageEnglish (US)
Article number104401
StatePublished - Jan 2023


  • COVID-19
  • Furin site
  • Immunogenic epitope
  • S protein
  • SARS-CoV-2

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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