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Chitinase 3-like-1 is a Therapeutic Target That Mediates the Effects of Aging in COVID-19 (preprint)
biorxiv; 2021.
Preprint
in English
| bioRxiv | ID: ppzbmed-10.1101.2021.01.05.425478
ABSTRACT
COVID-19 is caused by the SARS-CoV-2 (SC2) virus and is more prevalent and severe in the 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 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 demonstrated 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 coopts 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.
Full text:
Available
Collection:
Preprints
Database:
bioRxiv
Main subject:
Disease
/
COVID-19
Language:
English
Year:
2021
Document Type:
Preprint
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