PT  - JOURNAL ARTICLE
AU  - Suchitra Kamle
AU  - Bing Ma
AU  - Chang Min Lee
AU  - Gail Schor
AU  - Chun Geun Lee
AU  - Jack A. Elias
TI  - Host Chitinase 3-like-1 is a Universal Therapeutic Target for the Delta, Omicron and Other SARS-CoV-2 Viral Variants in COVID 19
AID  - 10.1101/2022.01.21.477274
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.01.21.477274
4099  - http://biorxiv.org/content/early/2022/01/24/2022.01.21.477274.short
4100  - http://biorxiv.org/content/early/2022/01/24/2022.01.21.477274.full
AB  - COVID 19 is the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2; SC2) which has caused a world-wide pandemic with striking morbidity and mortality. Evaluation of early SC2 strains suggested limited viral genetic diversity. However, genetic and epidemiologic investigations in the interim have revealed impressive genetic variability. Many of these viral variants are now defined as variants of concern (VOC) based on genetic alterations in their spike (S) and other proteins that cause enhanced transmissibility, decreased susceptibility to antibody neutralization or therapeutics and or their ability to induce severe disease. The delta (δ) and omicron (o) variants are particularly problematic based on their impressive and unprecedented transmissibility and ability to cause break through infections. The delta variant also accumulates at high concentrations in host tissues and has caused waves of lethal disease. SC2 infection is mediated by S protein binding to cellular ACE2 receptors and subsequent S protein protease processing. Because studies from our laboratory have demonstrated that chitinase 3-like-1 (CHI3L1) stimulates ACE2 and S priming proteases, 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.Competing Interest StatementJack A. Elias is a cofounder of Elkurt Pharmaceuticals and Ocean Biomedical which develop therapeutics based on the 18 glycosyl hydrolase gene family.