OpenLB
Open Library of Bioscience
Advanced Search
Signal transduction and targeted therapy
09 25, 2021;6 (1): 347.

CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 and its variants delta, alpha, beta, and gamma.

Jiejie Geng, Liang Chen, Yufeng Yuan, Ke Wang, Youchun Wang, Chuan Qin, Guizhen Wu, Ruo Chen, Zheng Zhang, Ding Wei, Peng Du, Jun Zhang, Peng Lin, Kui Zhang, Yongqiang Deng, Ke Xu, Jiangning Liu, Xiuxuan Sun, Ting Guo, Xu Yang, Jiao Wu, Jianli Jiang, Ling Li, Kun Zhang, Zhe Wang, Jing Zhang, Qingguo Yan, Hua Zhu, Zhaohui Zheng, Jinlin Miao, Xianghui Fu, Fengfan Yang, Xiaochun Chen, Hao Tang, Yang Zhang, Ying Shi, Yumeng Zhu, Zhuo Pei, Fei Huo, Xue Liang, Yatao Wang, Qingyi Wang, Wen Xie, Yirong Li, Mingyan Shi, Huijie Bian, Ping Zhu, Zhi-Nan Chen
Author Information
  1. Jiejie Geng: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  2. Liang Chen: School of Medicine, Shanghai University, Shanghai, 200444, China.
  3. Yufeng Yuan: Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
  4. Ke Wang: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  5. Youchun Wang: Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC) and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, 102629, China. ORCID
  6. Chuan Qin: Institute of Laboratory Animals Science, Chinese Academy of Medical Sciences, Beijing, 100071, China. ORCID
  7. Guizhen Wu: NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 100871, China.
  8. Ruo Chen: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  9. Zheng Zhang: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  10. Ding Wei: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  11. Peng Du: Beijing Institute of Biotechnology, Beijing, 100871, China.
  12. Jun Zhang: Beijing Institute of Biotechnology, Beijing, 100871, China. ORCID
  13. Peng Lin: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  14. Kui Zhang: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
  15. Yongqiang Deng: Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China. ORCID
  16. Ke Xu: NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 100871, China.
  17. Jiangning Liu: Institute of Laboratory Animals Science, Chinese Academy of Medical Sciences, Beijing, 100071, China.
  18. Xiuxuan Sun: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  19. Ting Guo: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  20. Xu Yang: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  21. Jiao Wu: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  22. Jianli Jiang: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  23. Ling Li: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  24. Kun Zhang: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  25. Zhe Wang: School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
  26. Jing Zhang: School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
  27. Qingguo Yan: School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
  28. Hua Zhu: Institute of Laboratory Animals Science, Chinese Academy of Medical Sciences, Beijing, 100071, China.
  29. Zhaohui Zheng: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
  30. Jinlin Miao: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  31. Xianghui Fu: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
  32. Fengfan Yang: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
  33. Xiaochun Chen: Jiangsu Pacific Meinuoke Biopharmceutical Co. Ltd, Changzhou, 213022, China.
  34. Hao Tang: Jiangsu Pacific Meinuoke Biopharmceutical Co. Ltd, Changzhou, 213022, China.
  35. Yang Zhang: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  36. Ying Shi: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  37. Yumeng Zhu: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  38. Zhuo Pei: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  39. Fei Huo: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  40. Xue Liang: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  41. Yatao Wang: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  42. Qingyi Wang: School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
  43. Wen Xie: Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
  44. Yirong Li: Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
  45. Mingyan Shi: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  46. Huijie Bian: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China. hjbian@fmmu.edu.cn. ORCID
  47. Ping Zhu: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China. zhuping@fmmu.edu.cn.
  48. Zhi-Nan Chen: National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China. znchen@fmmu.edu.cn.
PMID: 34564690 DOI: 10.1038/s41392-021-00760-8

Abstract

SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape, compromising the effectiveness of existing vaccines and neutralizing antibodies. An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants. Here, we identified CD147 as a universal receptor for SARS-CoV-2 and its variants. Meanwhile, Meplazeumab, a humanized anti-CD147 antibody, could block cellular entry of SARS-CoV-2 and its variants-alpha, beta, gamma, and delta, with inhibition rates of 68.7, 75.7, 52.1, 52.1, and 62.3% at 60 μg/ml, respectively. Furthermore, humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants, alpha and beta. When infected, these mice developed exudative alveolar pneumonia, featured by immune responses involving alveoli-infiltrated macrophages, neutrophils, and lymphocytes and activation of IL-17 signaling pathway. Mechanistically, we proposed that severe COVID-19-related cytokine storm is induced by a "spike protein-CD147-CyPA signaling axis": Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway, which further induced expression of cyclophilin A (CyPA); CyPA reciprocally bound to CD147 and triggered MAPK pathway. Consequently, the MAPK pathway regulated the expression of cytokines and chemokines, which promoted the development of cytokine storm. Importantly, Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants. Therefore, our findings provided a new perspective for severe COVID-19-related pathogenesis. Furthermore, the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment.

References

  1. Cell Signal. 2020 Jan;65:109413 [PMID: 31494257]
  2. Lancet Microbe. 2021 Jul;2(7):e283-e284 [PMID: 33846703]
  3. N Engl J Med. 2020 Apr 30;382(18):1708-1720 [PMID: 32109013]
  4. Antioxid Redox Signal. 2010 Mar 1;12(5):675-82 [PMID: 19747062]
  5. Front Cell Infect Microbiol. 2021 Feb 26;11:624483 [PMID: 33718270]
  6. Lancet Oncol. 2020 Jul;21(7):893-903 [PMID: 32479790]
  7. Mol Cells. 2021 Jun 30;44(6):384-391 [PMID: 34098591]
  8. Allergy. 2020 Nov;75(11):2829-2845 [PMID: 32496587]
  9. J Clin Microbiol. 2021 Jun 18;59(7):e0074121 [PMID: 33952596]
  10. Respir Res. 2021 Jan 29;22(1):32 [PMID: 33514373]
  11. Cell Rep. 2019 Apr 16;27(3):793-805.e4 [PMID: 30995477]
  12. Science. 2020 Aug 7;369(6504):718-724 [PMID: 32661059]
  13. Cell Rep Med. 2022 Jul 19;3(7):100680 [PMID: 35839768]
  14. Med Drug Discov. 2021 Jun;10:100086 [PMID: 33681755]
  15. Clin Transl Immunology. 2021 Feb 22;10(2):e1241 [PMID: 33628442]
  16. Br J Haematol. 2021 Oct;195(1):90-94 [PMID: 34101171]
  17. Science. 2002 Dec 6;298(5600):1911-2 [PMID: 12471242]
  18. Cell Host Microbe. 2020 Jul 8;28(1):124-133.e4 [PMID: 32485164]
  19. Med Sci Monit. 2020 Sep 15;26:e922979 [PMID: 32931486]
  20. J Biol Chem. 2011 Mar 11;286(10):8197-8203 [PMID: 21245143]
  21. Cell Mol Immunol. 2021 Apr;18(4):945-953 [PMID: 33637958]
  22. Virchows Arch. 2021 Mar;478(3):471-485 [PMID: 32989525]
  23. J Med Virol. 2021 Jan;93(1):250-256 [PMID: 32592501]
  24. Signal Transduct Target Ther. 2021 May 17;6(1):194 [PMID: 34001849]
  25. J Inflamm Res. 2020 Oct 06;13:673-680 [PMID: 33116747]
  26. Science. 2012 Nov 16;338(6109):975-80 [PMID: 22983707]
  27. J Virol. 2007 Jan;81(2):813-21 [PMID: 17079315]
  28. J Microbiol Immunol Infect. 2020 Jun;53(3):368-370 [PMID: 32205092]
  29. Med Drug Discov. 2020 Sep;7:100056 [PMID: 32835213]
  30. Nature. 2021 Aug;596(7870):103-108 [PMID: 34153975]
  31. Curr Med Chem. 2014;21(19):2138-45 [PMID: 24372217]
  32. Proc Natl Acad Sci U S A. 2021 May 11;118(19): [PMID: 33893175]
  33. Immunology. 2020 Jul;160(3):261-268 [PMID: 32460357]
  34. Viruses. 2021 May 21;13(6): [PMID: 34064066]
  35. Cancer. 2006 May 15;106(10):2284-94 [PMID: 16604531]
  36. J Pak Med Assoc. 2021 Mar;71(3):1033-1038 [PMID: 34057973]
  37. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3511-5 [PMID: 1565646]
  38. N Engl J Med. 2020 Feb 20;382(8):692-694 [PMID: 31978293]
  39. Signal Transduct Target Ther. 2020 Dec 4;5(1):283 [PMID: 33277466]
  40. Int J Mol Sci. 2021 Apr 26;22(9): [PMID: 33926110]
  41. Front Pharmacol. 2021 Mar 02;11:598128 [PMID: 33737877]
  42. Eur J Med Res. 2021 Jun 8;26(1):51 [PMID: 34103090]
  43. Methods Mol Biol. 2015;1282:1-23 [PMID: 25720466]
  44. J Leukoc Biol. 2017 Oct;102(4):989-992 [PMID: 28729360]
  45. Front Immunol. 2020 Oct 28;11:545980 [PMID: 33193313]
  46. Inflammation. 2017 Oct;40(5):1761-1772 [PMID: 28756520]
  47. PLoS Pathog. 2021 Jan 19;17(1):e1009195 [PMID: 33465158]
  48. Clin Rheumatol. 2018 Jan;37(1):59-66 [PMID: 28948414]
  49. Indian J Endocrinol Metab. 2020 Sep-Oct;24(5):381-386 [PMID: 33489841]

MeSH Term

Angiotensin-Converting Enzyme 2
Animals
Antibodies, Monoclonal, Humanized
Basigin
COVID-19
Chlorocebus aethiops
Cytokine Release Syndrome
Humans
MAP Kinase Signaling System
Mice
Mice, Transgenic
SARS-CoV-2
Vero Cells
COVID-19 Drug Treatment

Chemicals

Antibodies, Monoclonal, Humanized
BSG protein, human
meplazumab
Basigin
ACE2 protein, human
Angiotensin-Converting Enzyme 2
Journal Article Research Support, Non-U.S. Gov't

Links to CNCB-NGDC Resources

GEN: GEND000365 (RNA-seq Analysis of wild type, hACE2 and hCD147 mice lung tissues Transcriptomes after infection with SARS-CoV-2)

Word Cloud

Similar Articles

Cited By