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ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury

Author

Listed:
  • Tomokazu Yamaguchi

    (Akita University Graduate School of Medicine)

  • Midori Hoshizaki

    (Akita University Graduate School of Medicine
    National Institute of Biomedical Innovation, Health and Nutrition (NIBIOHN))

  • Takafumi Minato

    (Akita University Graduate School of Medicine)

  • Satoru Nirasawa

    (Japan International Research Center for Agricultural Sciences)

  • Masamitsu N. Asaka

    (Tsukuba Primate Research Center, NIBIOHN)

  • Mayumi Niiyama

    (Laboratory of Biopharmaceutical Research, NIBIOHN)

  • Masaki Imai

    (University of Tokyo)

  • Akihiko Uda

    (National Institute of Infectious Diseases)

  • Jasper Fuk-Woo Chan

    (The University of Hong Kong)

  • Saori Takahashi

    (Akita Research Institute of Food and Brewing)

  • Jianbo An

    (Akita University Graduate School of Medicine)

  • Akari Saku

    (Akita University Graduate School of Medicine)

  • Ryota Nukiwa

    (National Institute of Biomedical Innovation, Health and Nutrition (NIBIOHN)
    Osaka University Graduate School of Medicine)

  • Daichi Utsumi

    (Tsukuba Primate Research Center, NIBIOHN)

  • Maki Kiso

    (University of Tokyo)

  • Atsuhiro Yasuhara

    (University of Tokyo)

  • Vincent Kwok-Man Poon

    (The University of Hong Kong)

  • Chris Chung-Sing Chan

    (The University of Hong Kong)

  • Yuji Fujino

    (Osaka University Graduate School of Medicine)

  • Satoru Motoyama

    (Akita University Graduate School of Medicine)

  • Satoshi Nagata

    (Laboratory of Antibody Design, NIBIOHN)

  • Josef M. Penninger

    (University of British Columbia
    IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences)

  • Haruhiko Kamada

    (Laboratory of Biopharmaceutical Research, NIBIOHN)

  • Kwok-Yung Yuen

    (The University of Hong Kong)

  • Wataru Kamitani

    (Gunma University)

  • Ken Maeda

    (National Institute of Infectious Diseases)

  • Yoshihiro Kawaoka

    (University of Tokyo)

  • Yasuhiro Yasutomi

    (Tsukuba Primate Research Center, NIBIOHN)

  • Yumiko Imai

    (National Institute of Biomedical Innovation, Health and Nutrition (NIBIOHN))

  • Keiji Kuba

    (Akita University Graduate School of Medicine)

Abstract

Angiotensin-converting enzyme 2 (ACE2) is a receptor for cell entry of SARS-CoV-2, and recombinant soluble ACE2 protein inhibits SARS-CoV-2 infection as a decoy. ACE2 is a carboxypeptidase that degrades angiotensin II, thereby improving the pathologies of cardiovascular disease or acute lung injury. Here we show that B38-CAP, an ACE2-like enzyme, is protective against SARS-CoV-2-induced lung injury. Endogenous ACE2 expression is downregulated in the lungs of SARS-CoV-2-infected hamsters, leading to elevation of angiotensin II levels. Recombinant Spike also downregulates ACE2 expression and worsens the symptoms of acid-induced lung injury. B38-CAP does not neutralize cell entry of SARS-CoV-2. However, B38-CAP treatment improves the pathologies of Spike-augmented acid-induced lung injury. In SARS-CoV-2-infected hamsters or human ACE2 transgenic mice, B38-CAP significantly improves lung edema and pathologies of lung injury. These results provide the first in vivo evidence that increasing ACE2-like enzymatic activity is a potential therapeutic strategy to alleviate lung pathologies in COVID-19 patients.

Suggested Citation

  • Tomokazu Yamaguchi & Midori Hoshizaki & Takafumi Minato & Satoru Nirasawa & Masamitsu N. Asaka & Mayumi Niiyama & Masaki Imai & Akihiko Uda & Jasper Fuk-Woo Chan & Saori Takahashi & Jianbo An & Akari , 2021. "ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27097-8
    DOI: 10.1038/s41467-021-27097-8
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    as
    1. Zhen Zou & Yiwu Yan & Yuelong Shu & Rongbao Gao & Yang Sun & Xiao Li & Xiangwu Ju & Zhu Liang & Qiang Liu & Yan Zhao & Feng Guo & Tian Bai & Zongsheng Han & Jindong Zhu & Huandi Zhou & Fengming Huang , 2014. "Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections," Nature Communications, Nature, vol. 5(1), pages 1-7, May.
    2. Peng Zhou & Xing-Lou Yang & Xian-Guang Wang & Ben Hu & Lei Zhang & Wei Zhang & Hao-Rui Si & Yan Zhu & Bei Li & Chao-Lin Huang & Hui-Dong Chen & Jing Chen & Yun Luo & Hua Guo & Ren-Di Jiang & Mei-Qin L, 2020. "Addendum: A pneumonia outbreak associated with a new coronavirus of probable bat origin," Nature, Nature, vol. 588(7836), pages 6-6, December.
    3. Peng Zhou & Xing-Lou Yang & Xian-Guang Wang & Ben Hu & Lei Zhang & Wei Zhang & Hao-Rui Si & Yan Zhu & Bei Li & Chao-Lin Huang & Hui-Dong Chen & Jing Chen & Yun Luo & Hua Guo & Ren-Di Jiang & Mei-Qin L, 2020. "A pneumonia outbreak associated with a new coronavirus of probable bat origin," Nature, Nature, vol. 579(7798), pages 270-273, March.
    4. Takafumi Minato & Satoru Nirasawa & Teruki Sato & Tomokazu Yamaguchi & Midori Hoshizaki & Tadakatsu Inagaki & Kazuhiko Nakahara & Tadashi Yoshihashi & Ryo Ozawa & Saki Yokota & Miyuki Natsui & Souichi, 2020. "B38-CAP is a bacteria-derived ACE2-like enzyme that suppresses hypertension and cardiac dysfunction," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    5. Michael A. Crackower & Renu Sarao & Gavin Y. Oudit & Chana Yagil & Ivona Kozieradzki & Sam E. Scanga & Antonio J. Oliveira-dos-Santos & Joan da Costa & Liyong Zhang & York Pei & James Scholey & Carlos, 2002. "Angiotensin-converting enzyme 2 is an essential regulator of heart function," Nature, Nature, vol. 417(6891), pages 822-828, June.
    6. Yumiko Imai & Keiji Kuba & Shuan Rao & Yi Huan & Feng Guo & Bin Guan & Peng Yang & Renu Sarao & Teiji Wada & Howard Leong-Poi & Michael A. Crackower & Akiyoshi Fukamizu & Chi-Chung Hui & Lutz Hein & S, 2005. "Angiotensin-converting enzyme 2 protects from severe acute lung failure," Nature, Nature, vol. 436(7047), pages 112-116, July.
    7. Jian Shang & Gang Ye & Ke Shi & Yushun Wan & Chuming Luo & Hideki Aihara & Qibin Geng & Ashley Auerbach & Fang Li, 2020. "Structural basis of receptor recognition by SARS-CoV-2," Nature, Nature, vol. 581(7807), pages 221-224, May.
    8. Robbert Boudewijns & Hendrik Jan Thibaut & Suzanne J. F. Kaptein & Rong Li & Valentijn Vergote & Laura Seldeslachts & Johan Weyenbergh & Carolien Keyzer & Lindsey Bervoets & Sapna Sharma & Laurens Lie, 2020. "STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    9. Wenhui Li & Michael J. Moore & Natalya Vasilieva & Jianhua Sui & Swee Kee Wong & Michael A. Berne & Mohan Somasundaran & John L. Sullivan & Katherine Luzuriaga & Thomas C. Greenough & Hyeryun Choe & M, 2003. "Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus," Nature, Nature, vol. 426(6965), pages 450-454, November.
    10. Linlin Bao & Wei Deng & Baoying Huang & Hong Gao & Jiangning Liu & Lili Ren & Qiang Wei & Pin Yu & Yanfeng Xu & Feifei Qi & Yajin Qu & Fengdi Li & Qi Lv & Wenling Wang & Jing Xue & Shuran Gong & Mingy, 2020. "The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice," Nature, Nature, vol. 583(7818), pages 830-833, July.
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