Drugs, Metabolites, and Lung Accumulating Small Lysosomotropic Molecules: Multiple Targeting Impedes SARS-CoV-2 Infection and Progress to COVID-19.
Drugs, Metabolites, and Lung Accumulating Small Lysosomotropic Molecules: Multiple Targeting Impedes SARS-CoV-2 Infection and Progress to COVID-19.
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DOI：
10.3390/ijms22041797
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发表时间：
2021-02-11
影响因子：
5.6
通讯作者：
Deigner HP
中科院分区：
文献类型：
--
作者：
Blaess M;Kaiser L;Sommerfeld O;Csuk R;Deigner HP
溶酶体性是小分子的生物学特征，独立于其内在药理作用。一般来说，溶酶体化合物会影响各种靶标，例如源自溶酶体酶的脂质第二信使，促进全身炎症中的内皮应激反应；炎症信使，例如 IL-6；和组织蛋白酶 L 依赖性病毒进入宿主细胞。这组异质药物和活性代谢物包括各种有前景的候选药物，在预防和治疗严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染/2019 冠状病毒病 (COVID-19) 和由细菌或病毒感染引发的细胞因子释放综合征 (CRS) 方面，其药物特性比最初考虑的（羟基）氯喹更有利。在这一假设中，我们讨论了溶酶体趋性、肺组织溶酶体富集、SARS-CoV-2 感染和向 COVID-19 转变之间的可能关系。此外，我们根据合理的资格标准，根据更有利的药物概况，推断出进一步合适的已批准药物和活性代谢物，包括现成的非处方药（OTC）。对已经因其他已有疾病而接受溶酶体药物治疗的患者的益处强调了这些药物在当前 SARS-CoV2/COVID-19 大流行中的重要临床意义。
Lysosomotropism is a biological characteristic of small molecules, independently present of their intrinsic pharmacological effects. Lysosomotropic compounds, in general, affect various targets, such as lipid second messengers originating from lysosomal enzymes promoting endothelial stress response in systemic inflammation; inflammatory messengers, such as IL-6; and cathepsin L-dependent viral entry into host cells. This heterogeneous group of drugs and active metabolites comprise various promising candidates with more favorable drug profiles than initially considered (hydroxy) chloroquine in prophylaxis and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections/Coronavirus disease 2019 (COVID-19) and cytokine release syndrome (CRS) triggered by bacterial or viral infections. In this hypothesis, we discuss the possible relationships among lysosomotropism, enrichment in lysosomes of pulmonary tissue, SARS-CoV-2 infection, and transition to COVID-19. Moreover, we deduce further suitable approved drugs and active metabolites based with a more favorable drug profile on rational eligibility criteria, including readily available over-the-counter (OTC) drugs. Benefits to patients already receiving lysosomotropic drugs for other pre-existing conditions underline their vital clinical relevance in the current SARS-CoV2/COVID-19 pandemic.
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β-核心就是使用溶酶体进行出口，而不是生物合成分泌途径。
影响因子：
64.5
作者：
Ghosh S;Dellibovi-Ragheb TA;Kerviel A;Pak E;Qiu Q;Fisher M;Takvorian PM;Bleck C;Hsu VW;Fehr AR;Perlman S;Achar SR;Straus MR;Whittaker GR;de Haan CAM;Kehrl J;Altan-Bonnet G;Altan-Bonnet N
通讯作者：
Altan-Bonnet N
影响因子：
2.5
作者：
Brockbals, Lana;Staeheli, Sandra N.;Steuer, Andrea E.
通讯作者：
Steuer, Andrea E.
影响因子：
4.9
作者：
Dyall, Julie;Coleman, Christopher M.;Frieman, Matthew B.
通讯作者：
Frieman, Matthew B.
影响因子：
6.1
作者：
BICKEL, MH;GRABER, BE;MOOR, M
通讯作者：
MOOR, M
影响因子：
4.8
作者：
Ballout, Rami A.;Sviridov, Dmitri;Remaley, Alan T.
通讯作者：
Remaley, Alan T.