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ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury.
Yamaguchi, Tomokazu; Hoshizaki, Midori; Minato, Takafumi; Nirasawa, Satoru; Asaka, Masamitsu N; Niiyama, Mayumi; Imai, Masaki; Uda, Akihiko; Chan, Jasper Fuk-Woo; Takahashi, Saori; An, Jianbo; Saku, Akari; Nukiwa, Ryota; Utsumi, Daichi; Kiso, Maki; Yasuhara, Atsuhiro; Poon, Vincent Kwok-Man; Chan, Chris Chung-Sing; Fujino, Yuji; Motoyama, Satoru; Nagata, Satoshi; Penninger, Josef M; Kamada, Haruhiko; Yuen, Kwok-Yung; Kamitani, Wataru; Maeda, Ken; Kawaoka, Yoshihiro; Yasutomi, Yasuhiro; Imai, Yumiko; Kuba, Keiji.
  • Yamaguchi T; Department of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
  • Hoshizaki M; Department of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
  • Minato T; Laboratory of Regulation of Intractable Infectious Diseases, National Institute of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan.
  • Nirasawa S; Department of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
  • Asaka MN; Biological Resources and Post-Harvest Division, Japan International Research Center for Agricultural Sciences, 1-1 Ohwashi, Tsukuba, Ibaraki, 305-8686, Japan.
  • Niiyama M; Tsukuba Primate Research Center, NIBIOHN, Hachimandai 1-1, Tsukuba-shi, Ibaraki, 305-0843, Japan.
  • Imai M; Laboratory of Biopharmaceutical Research, NIBIOHN, 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan.
  • Uda A; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 108-8639, Tokyo, Japan.
  • Chan JF; Department of Veterinary Science, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjyuku-ku, Tokyo, 162-8640, Japan.
  • Takahashi S; State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  • An J; Akita Research Institute of Food and Brewing, 4-26 Sanuki, Arayamachi, Akita, 010-1623, Japan.
  • Saku A; Department of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
  • Nukiwa R; Department of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
  • Utsumi D; Laboratory of Regulation of Intractable Infectious Diseases, National Institute of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan.
  • Kiso M; Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan.
  • Yasuhara A; Tsukuba Primate Research Center, NIBIOHN, Hachimandai 1-1, Tsukuba-shi, Ibaraki, 305-0843, Japan.
  • Poon VK; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 108-8639, Tokyo, Japan.
  • Chan CC; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 108-8639, Tokyo, Japan.
  • Fujino Y; State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  • Motoyama S; State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  • Nagata S; Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan.
  • Penninger JM; Department of Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
  • Kamada H; Laboratory of Antibody Design, NIBIOHN, 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan.
  • Yuen KY; Department of Medical Genetics, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
  • Kamitani W; IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030, Vienna, Austria.
  • Maeda K; Laboratory of Biopharmaceutical Research, NIBIOHN, 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan.
  • Kawaoka Y; State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  • Yasutomi Y; Department of Infectious Diseases and Host Defense, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan.
  • Imai Y; Department of Veterinary Science, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjyuku-ku, Tokyo, 162-8640, Japan.
  • Kuba K; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 108-8639, Tokyo, Japan.
Nat Commun ; 12(1): 6791, 2021 11 23.
Article in English | MEDLINE | ID: covidwho-1532053
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Internalization / Lung Injury / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 / COVID-19 Drug Treatment Limits: Animals / Female / Humans / Male Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-27097-8

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Internalization / Lung Injury / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 / COVID-19 Drug Treatment Limits: Animals / Female / Humans / Male Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-27097-8