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

Autor: Daichi Utsumi, Akari Saku, Yoshihiro Kawaoka, Kwok-Yung Yuen, Chris Chung-Sing Chan, Satoru Motoyama, Saori Takahashi, Jasper Fuk-Woo Chan, Jianbo An, Takafumi Minato, Satoshi Nagata, Vincent Kwok-Man Poon, Masaki Imai, Keiji Kuba, Maki Kiso, Midori Hoshizaki, Atsuhiro Yasuhara, Josef M. Penninger, Tomokazu Yamaguchi, Ken Maeda, Yasuhiro Yasutomi, Yumiko Imai, Haruhiko Kamada, Mayumi Niiyama, Akihiko Uda, Ryota Nukiwa, Masamitsu N Asaka, Satoru Nirasawa, Wataru Kamitani, Yuji Fujino
Rok vydání: 2021
Předmět:
Male
viruses
General Physics and Astronomy
Endogeny
Carboxypeptidases
Pharmacology
Mice
Cricetinae
Chlorocebus aethiops
skin and connective tissue diseases
Receptor
Lung
Multidisciplinary
biology
Angiotensin II
Lung Injury
respiratory system
medicine.anatomical_structure
Spike Glycoprotein
Coronavirus
Female
Angiotensin-Converting Enzyme 2
hormones
hormone substitutes
and hormone antagonists
Genetically modified mouse
Respiratory distress syndrome
Science
Acute Lung Injury
Mice
Transgenic
Pulmonary Edema
Lung injury
Article
General Biochemistry
Genetics and Molecular Biology
In vivo
medicine
Animals
Humans
Vero Cells
SARS-CoV-2
business.industry
fungi
COVID-19
General Chemistry
Virus Internalization
Carboxypeptidase
COVID-19 Drug Treatment
respiratory tract diseases
Disease Models
Animal
biology.protein
Peptides
business
Zdroj: Nature Communications, Vol 12, Iss 1, Pp 1-13 (2021)
Nature Communications
ISSN: 2041-1723
DOI: 10.1038/s41467-021-27097-8
Popis: 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.
Endogenous ACE2 is a receptor for SARS-CoV-2 and a recombinant soluble ACE2 protein can inhibit SARS-CoV-2 infection acting as a decoy. Here the authors show that B38-CAP, an ACE2-like enzyme but not a decoy for the virus, is protective against SARS-CoV-2-induced lung injury in animal models.
Databáze: OpenAIRE
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