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治疗 2019-nCoV 相关传染病的现有苦味药物。

Existing bitter medicines for fighting 2019-nCoV-associated infectious diseases.

机构信息

Department of Endocrinology, Shanghai Gongli Hospital, The Second Military Medical University, Shanghai, China.

State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

出版信息

FASEB J. 2020 May;34(5):6008-6016. doi: 10.1096/fj.202000502. Epub 2020 Apr 13.

Abstract

The sudden outbreak of COVID-19 has led to more than seven thousand deaths. Unfortunately, there are no specific drugs available to cure this disease. Type 2 taste receptors (TAS2Rs) may play an important role in host defense mechanisms. Based on the idea of host-directed therapy (HDT), we performed a negative co-expression analysis using big data of 60 000 Affymetrix expression arrays and 5000 TCGA data sets to determine the functions of TAS2R10, which can be activated by numerous bitter substances. Excitingly, we found that the main functions of TAS2R10 involved controlling infectious diseases caused by bacteria, viruses, and parasites, suggesting that TAS2R10 is a key trigger of host defense pathways. To quickly guide the clinical treatment of 2019-nCoV, we searched currently available drugs that are agonists of TAS2Rs. We identified many cheap, available, and safe medicines, such as diphenidol, quinine, chloroquine, artemisinin, chlorpheniramine, yohimbine, and dextromethorphan, which may target the most common symptoms caused by 2019-nCoV. We suggest that a cocktail-like recipe of existing bitter drugs may help doctors to fight this catastrophic disease and that the general public may drink or eat bitter substances, such as coffee, tea, or bitter vegetables, to reduce the risk of infection.

摘要

COVID-19 的突然爆发导致了超过 7000 人死亡。不幸的是,目前还没有专门治疗这种疾病的药物。TAS2R10 可被多种苦味物质激活,我们基于宿主导向治疗(HDT)的理念,使用 60000 个 Affymetrix 表达谱和 5000 个 TCGA 数据集的大数据进行负共表达分析,以确定 TAS2R10 的功能。令人兴奋的是,我们发现 TAS2R10 的主要功能涉及控制由细菌、病毒和寄生虫引起的传染病,表明 TAS2R10 是宿主防御途径的关键触发因素。为了快速指导 2019-nCoV 的临床治疗,我们搜索了目前可用的 TAS2R 激动剂类药物。我们确定了许多便宜、易得、安全的药物,如苯海拉明、奎宁、氯喹、青蒿素、氯苯那敏、育亨宾和右美沙芬等,这些药物可能针对 2019-nCoV 引起的最常见症状。我们建议使用现有的苦味药物鸡尾酒疗法可能有助于医生对抗这种灾难性疾病,公众也可以饮用或食用咖啡、茶或苦味蔬菜等苦味物质,以降低感染风险。

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