Host chitinase 3-like-1 is a universal therapeutic target for SARS-CoV-2 viral variants in COVID-19.
Host chitinase 3-like-1 is a universal therapeutic target for SARS-CoV-2 viral variants in COVID-19.
复制标题
DOI：
10.7554/elife.78273
复制
发表时间：
2022-06-23
期刊：
影响因子：
7.7
通讯作者：
Elias, Jack A
中科院分区：
文献类型：
--
作者：
Kamle, Suchitra;Ma, Bing;Lee, Chang Min;Schor, Gail;Zhou, Yang;Lee, Chun Geun;Elias, Jack A
2019年冠状病毒病（COVID-19）是由严重急性呼吸综合征冠状病毒2（SARS-CoV-2; SC2）引起的疾病，已引起全球大流行，发病率和死亡率惊人。对SC2毒株的评价显示出令人印象深刻的遗传变异性，其中许多病毒变体现在被定义为引起传播性增强、对抗体中和或治疗剂的敏感性降低和/或诱导严重疾病的能力的关注变体（VOC）。目前，delta（δ）和omicron（o）变体特别有问题，因为它们具有令人印象深刻的和前所未有的传播性以及引起突破性感染的能力。δ变体也在宿主组织中以高浓度积累，并引起致命疾病的浪潮。由于我们实验室的研究已经证明几丁质酶3样-1（CHI 3L 1）刺激介导SC2感染的ACE 2和Spike（S）引发蛋白酶，因此进行了研究以确定靶向CHI 3L 1的干预是否是SC2病毒变体感染的有效抑制剂。在这里，我们证明，CHI 3L 1增强上皮细胞感染的假病毒表达的α，β，γ，δ，或omicron S蛋白和CHI 3L 1抑制剂抗CHI 3L 1和春雷霉素抑制上皮细胞感染这些VOC假病毒部分。因此，CHI 3L 1是COVID-19中的通用、VOC非依赖性治疗靶标。
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.