Chitinase 3-like-1 is a Therapeutic Target That Mediates the Effects of Aging in COVID-19

Kamle, S.; Ma, B.; He, C. H.; Akosman, B.; Zhou, Y.; Lee, C.-M.; El-Deiry, W. S.; Huntington, K.; Liang, O.; Machan, J. T.; Kang, M.-J.; Shin, H. J.; Mizoguchi, E.; Lee, C. G.; Elias, J. A.

doi:10.1101/2021.01.05.425478

bioRxiv · 10.1101/2021.01.05.425478

Chitinase 3-like-1 is a Therapeutic Target That Mediates the Effects of Aging in COVID-19

Kamle, S.·Ma, B.·He, C. H.·Akosman, B.·Zhou, Y.·Lee, C.-M.·El-Deiry, W. S.·Huntington, K.·Liang, O.·Machan, J. T.·Kang, M.-J.·Shin, H. J.·Mizoguchi, E.·Lee, C. G.·Elias, J. A.

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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.

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Kamle, S., Ma, B., He, C. H., Akosman, B., Zhou, Y., Lee, C.-M., El-Deiry, W. S., Huntington, K., Liang, O., Machan, J. T., Kang, M.-J., Shin, H. J., Mizoguchi, E., Lee, C. G., Elias, J. A.. 2021-01-06. Chitinase 3-like-1 is a Therapeutic Target That Mediates the Effects of Aging in COVID-19. https://doi.org/10.1101/2021.01.05.425478

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