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用于评估组织蛋白酶作为 COVID-19 宿主靶标的细胞外基质生物传感模拟物。

An extracellular matrix biosensing mimetic for evaluating cathepsin as a host target for COVID-19.

机构信息

School of Biological Science and Technology, University of Jinan, 336 West Road of Nan, Xinzhuang, 250022, China; Shandong Keyuan Pharmaceutical Co., Ltd, 250022, China.

School of Biological Science and Technology, University of Jinan, 336 West Road of Nan, Xinzhuang, 250022, China.

出版信息

Anal Chim Acta. 2022 Sep 8;1225:340267. doi: 10.1016/j.aca.2022.340267. Epub 2022 Aug 16.

Abstract

To combat the new virus currently ravaging the whole world, every possible anti-virus strategy should be explored. As the main strategy of targeting the virus itself is being frustrated by the rapid mutation of the virus, people are seeking an alternative "host targeting" strategy: neutralizing proteins in the human body that cooperate with the virus. The cathepsin family is such a group of promising host targets, the main biological function of which is to digest the extracellular matrix (ECM) to clear a path for virus spreading. To evaluate the potential of cathepsin as a host target, we have constructed a biosensing interface mimicking the ECM, which can detect cathepsin from 3.3 pM to 33 nM with the limit of detection of 1 pM. Based on our quantitative analysis enabled by this biosensing interface, it is clear that patients with background diseases such as chronic inflammation and tumor, tend to have higher cathepsin activity, confirming the potential of cathepsin to serve as a host target for combating COVID-19 virus.

摘要

为了应对目前肆虐全球的新型病毒,我们应该探索一切可能的抗病毒策略。由于针对病毒本身的主要策略因病毒的快速突变而受挫,人们正在寻找一种替代的“宿主靶向”策略:中和与病毒合作的人体内的蛋白质。组织蛋白酶家族就是这样一组很有前途的宿主靶标,其主要生物学功能是消化细胞外基质 (ECM) 以清除病毒传播的途径。为了评估组织蛋白酶作为宿主靶标的潜力,我们构建了一种模拟 ECM 的生物传感界面,可以检测 3.3 pM 至 33 nM 的组织蛋白酶,检测限为 1 pM。基于我们通过该生物传感界面进行的定量分析,患有慢性炎症和肿瘤等背景疾病的患者往往具有更高的组织蛋白酶活性,这证实了组织蛋白酶作为对抗 COVID-19 病毒的宿主靶标的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/026c/9380907/bc68f03d031a/ga1_lrg.jpg

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