Tissue- and cell-expression of druggable host proteins provide insights into repurposing drugs for COVID-19.
Tissue- and cell-expression of druggable host proteins provide insights into repurposing drugs for COVID-19.
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DOI：
10.1111/cts.13400
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发表时间：
2022-12
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影响因子：
--
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中科院分区：
文献类型：
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几种人类宿主蛋白在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的生命周期中发挥重要作用。许多靶向这些宿主蛋白质的药物已被研究作为2019冠状病毒病（COVID-19）的潜在治疗药物。使用从人类蛋白质图谱、蛋白质组学数据库、人类蛋白质组图谱数据库和临床COVID-19研究中检索的蛋白质组学数据，总结了选定宿主蛋白质的组织特异性表达。根据近年来蛋白质组学研究的进展，总结了不同细胞系的蛋白质表达特征。从体外研究中收集半最大有效浓度或半最大抑制浓度值。药代动力学数据主要来自健康受试者或非COVID-19患者的研究。对于几种宿主蛋白，观察到相当多的组织特异性表达模式。肺中的ACE 2表达显著低于许多其他组织（例如，肾和肠）;肺中的TMPRSS 2表达显著低于其它组织（例如，前列腺和肠）。肺中内吞相关蛋白CTSL、CLTC、NPC 1和PIKfyve的表达水平与大多数其他组织相当或高于大多数其他组织。TMPRSS 2表达在细胞系之间存在显著差异，这可能与几种药物的细胞依赖性抗病毒活性有关。药物释放受体ICAM 1和CTSB在肺中的表达水平高于其他组织。总之，细胞和组织特异性蛋白质组学数据可以帮助解释宿主导向药物在各种细胞中的体外抗病毒活性，并帮助将体外发现转化为临床研究，以开发安全有效的COVID-19治疗方法。
Several human host proteins play important roles in the lifecycle of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Many drugs targeting these host proteins have been investigated as potential therapeutics for coronavirus disease 2019 (COVID‐19). The tissue‐specific expressions of selected host proteins were summarized using proteomics data retrieved from the Human Protein Atlas, ProteomicsDB, Human Proteome Map databases, and a clinical COVID‐19 study. Protein expression features in different cell lines were summarized based on recent proteomics studies. The half‐maximal effective concentration or half‐maximal inhibitory concentration values were collected from in vitro studies. The pharmacokinetic data were mainly from studies in healthy subjects or non‐COVID‐19 patients. Considerable tissue‐specific expression patterns were observed for several host proteins. ACE2 expression in the lungs was significantly lower than in many other tissues (e.g., the kidneys and intestines); TMPRSS2 expression in the lungs was significantly lower than in other tissues (e.g., the prostate and intestines). The expression levels of endocytosis‐associated proteins CTSL, CLTC, NPC1, and PIKfyve in the lungs were comparable to or higher than most other tissues. TMPRSS2 expression was markedly different between cell lines, which could be associated with the cell‐dependent antiviral activities of several drugs. Drug delivery receptor ICAM1 and CTSB were expressed at a higher level in the lungs than in other tissues. In conclusion, the cell‐ and tissue‐specific proteomics data could help interpret the in vitro antiviral activities of host‐directed drugs in various cells and aid the transition of the in vitro findings to clinical research to develop safe and effective therapeutics for COVID‐19.
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影响因子：
4.4
作者：
Foster MW;Gwinn WM;Kelly FL;Brass DM;Valente AM;Moseley MA;Thompson JW;Morgan DL;Palmer SM
通讯作者：
Palmer SM
影响因子：
8.8
作者：
Dittmar M;Lee JS;Whig K;Segrist E;Li M;Kamalia B;Castellana L;Ayyanathan K;Cardenas-Diaz FL;Morrisey EE;Truitt R;Yang W;Jurado K;Samby K;Ramage H;Schultz DC;Cherry S
通讯作者：
Cherry S
影响因子：
64.8
作者：
Cote, Marceline;Misasi, John;Ren, Tao;Bruchez, Anna;Lee, Kyungae;Filone, Claire Marie;Hensley, Lisa;Li, Qi;Ory, Daniel;Chandran, Kartik;Cunningham, James
通讯作者：
Cunningham, James
影响因子：
13.5
作者：
Flisiak, Robert;Horban, Andrzej;Scalfaro, Pietro
通讯作者：
Scalfaro, Pietro
影响因子：
4.6
作者：
Chittasupho, Chuda;Xie, Sheng-Xue;Baoum, Abdulgader;Yakovleva, Tatyana;Siahaan, Teruna J.;Berkland, Cory J.
通讯作者：
Berkland, Cory J.