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Chitinase 3-like-1 is a therapeutic target that mediates the effects of aging in COVID-19.
Kamle, Suchitra; Ma, Bing; He, Chuan Hua; Akosman, Bedia; Zhou, Yang; Lee, Chang-Min; El-Deiry, Wafik S; Huntington, Kelsey; Liang, Olin; Machan, Jason T; Kang, Min-Jong; Shin, Hyeon Jun; Mizoguchi, Emiko; Lee, Chun Geun; Elias, Jack A.
  • Kamle S; Molecular Microbiology and Immunology.
  • Ma B; Molecular Microbiology and Immunology.
  • He CH; Molecular Microbiology and Immunology.
  • Akosman B; Molecular Microbiology and Immunology.
  • Zhou Y; Molecular Microbiology and Immunology.
  • Lee CM; Molecular Microbiology and Immunology.
  • El-Deiry WS; Pathology and Laboratory Medicine.
  • Huntington K; Hematology-Oncology Division, Department of Medicine.
  • Liang O; The Joint Program in Cancer Biology.
  • Machan JT; Cancer Center at Brown University, and.
  • Kang MJ; Pathology and Laboratory Medicine.
  • Shin HJ; Hematology-Oncology Division, Department of Medicine.
  • Mizoguchi E; The Joint Program in Cancer Biology.
  • Lee CG; Cancer Center at Brown University, and.
  • Elias JA; Hematology-Oncology Division, Department of Medicine.
JCI Insight ; 6(21)2021 11 08.
Article in English | MEDLINE | ID: covidwho-1506181
Preprint
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ABSTRACT
COVID-19 is caused by SARS-CoV-2 (SC2) and is more prevalent and severe in elderly and patients with comorbid diseases (CM). Because chitinase 3-like-1 (CHI3L1) is induced during aging and CM, the relationships between CHI3L1 and SC2 were investigated. Here, we demonstrate that CHI3L1 is a potent stimulator of the SC2 receptor angiotensin converting enzyme 2 (ACE2) and viral spike protein priming proteases (SPP), that ACE2 and SPP are induced during aging, and that anti-CHI3L1, kasugamycin, and inhibitors of phosphorylation abrogate these ACE2- and SPP-inductive events. Human studies also demonstrate that the levels of circulating CHI3L1 are increased in the elderly and patients with CM, where they correlate with COVID-19 severity. These studies demonstrate that CHI3L1 is a potent stimulator of ACE2 and SPP, that this induction is a major mechanism contributing to the effects of aging during SC2 infection, and that CHI3L1 co-opts the CHI3L1 axis to augment SC2 infection. CHI3L1 plays a critical role in the pathogenesis of and is an attractive therapeutic target in COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Aging / Chitinase-3-Like Protein 1 / COVID-19 Type of study: Experimental Studies / Prognostic study Limits: Humans Language: English Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Aging / Chitinase-3-Like Protein 1 / COVID-19 Type of study: Experimental Studies / Prognostic study Limits: Humans Language: English Year: 2021 Document Type: Article