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Measurement of Chitinase Activity in Biological Samples
Published on: August 22, 2019
Host chitinase 3-like-1 is a universal therapeutic target for SARS-CoV-2 viral variants in COVID-19
Suchitra Kamle1, Bing Ma1, Chang Min Lee1
1Department of Molecular Microbiology and Immunology, Brown University, Providence, United States.
Abstract:
Coronavirus disease 2019 (COVID-19) is the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2; SC2), which has caused a worldwide pandemic with striking morbidity and mortality. Evaluation of SC2 strains demonstrated impressive genetic variability, and many of these viral variants are now defined as variants of concern (VOC) that cause enhanced transmissibility, decreased susceptibility to antibody neutralization or therapeutics, and/or the ability to induce severe disease. Currently, the delta (δ) and omicron (ο) variants are particularly problematic based on their impressive and unprecedented transmissibility and ability to cause breakthrough infections. The delta variant also accumulates at high concentrations in host tissues and has caused waves of lethal disease. Because studies from our laboratory have demonstrated that chitinase 3-like-1 (CHI3L1) stimulates ACE2 and Spike (S) priming proteases that mediate SC2 infection, studies were undertaken to determine if interventions that target CHI3L1 are effective inhibitors of SC2 viral variant infection. Here, we demonstrate that CHI3L1 augments epithelial cell infection by pseudoviruses that express the alpha, beta, gamma, delta, or omicron S proteins and that the CHI3L1 inhibitors anti-CHI3L1 and kasugamycin inhibit epithelial cell infection by these VOC pseudovirus moieties. Thus, CHI3L1 is a universal, VOC-independent therapeutic target in COVID-19.
Insights
Chitinase 3-like-1 (CHI3L1) enhances infection by COVID-19 variants. Targeting CHI3L1 with inhibitors effectively blocks infection by SARS-CoV-2 variants of concern, offering a universal therapeutic strategy.
Area of Science:
- Virology
- Immunology
- Biochemistry
Background:
- Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VOCs) exhibit increased transmissibility and immune evasion.
- Chitinase 3-like-1 (CHI3L1) is implicated in stimulating proteases essential for SARS-CoV-2 entry into host cells.
Purpose of the Study:
- To investigate if targeting CHI3L1 can inhibit infection by SARS-CoV-2 VOCs.
- To evaluate CHI3L1 as a universal therapeutic target against diverse viral variants.
Main Methods:
- Utilized pseudoviruses expressing spike proteins from various SARS-CoV-2 variants (Alpha, Beta, Gamma, Delta, Omicron).
- Assessed the effect of CHI3L1 on epithelial cell infection mediated by these pseudoviruses.
- Tested the efficacy of CHI3L1 inhibitors (anti-CHI3L1 antibody and kasugamycin) in blocking viral entry.
Main Results:
- CHI3L1 was found to augment epithelial cell infection by pseudoviruses from multiple SARS-CoV-2 VOCs.
- Both anti-CHI3L1 and kasugamycin demonstrated inhibitory effects on VOC pseudovirus infection.
- These findings indicate CHI3L1's role in facilitating infection across different viral variants.
Conclusions:
- Chitinase 3-like-1 (CHI3L1) is a key factor augmenting epithelial cell infection by SARS-CoV-2 variants of concern.
- CHI3L1 inhibitors, including anti-CHI3L1 and kasugamycin, effectively reduce infection by these variants.
- CHI3L1 represents a promising, universal therapeutic target for combating COVID-19, irrespective of the specific SARS-CoV-2 variant.
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