The lysosome: A potential juncture between SARS-CoV-2 infectivity and Niemann-Pick disease type C, with therapeutic implications
The lysosome: A potential juncture between SARS-CoV-2 infectivity and Niemann-Pick disease type C, with therapeutic implications
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DOI：
10.1096/fj.202000654r
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发表时间：
2020-05-05
期刊：
影响因子：
4.8
通讯作者：
Remaley, Alan T.
中科院分区：
文献类型：
--
作者：
Ballout, Rami A.;Sviridov, Dmitri;Remaley, Alan T.
在寻找可用于预防和/或治疗COVID-19的安全有效药物的竞赛中，药物再利用可能是最快的选择。通过描述新出现的冠状病毒SARS-CoV-2的生命周期，根据正在进行抗病毒测试的各种重新使用的抗菌剂的治疗效果的新数据，我们在这篇综述中强调了一些这些测试化合物之间可能的机制趋同。具体而言，我们认为羟氯喹和其他几种正在接受测试的药物的溶酶体效应可能是其体外抗COVID-19抗病毒活性的原因。此外，我们提出，尼曼匹克病C型（NPC），溶酶体储存障碍，可能提供新的见解，为SARS冠状病毒-2的潜在的未来治疗目标，通过突出的关键建立功能的障碍，共同导致一个“不利的”宿主细胞环境，可能会干扰病毒的传播。我们的推理是从先前与NPC相关的生化和细胞生物学发现，以及快速发展的COVID-19数据中演变而来的。我们的总体目标是表明，一般靶向溶酶体功能的药理学干预，以及那些特别能够可逆诱导瞬时NPC样细胞和生化表型的药理学干预，构成了可用于治疗靶向COVID-19的合理机制。
Drug repurposing is potentially the fastest available option in the race to identify safe and efficacious drugs that can be used to prevent and/or treat COVID-19. By describing the life cycle of the newly emergent coronavirus, SARS-CoV-2, in light of emerging data on the therapeutic efficacy of various repurposed antimicrobials undergoing testing against the virus, we highlight in this review a possible mechanistic convergence between some of these tested compounds. Specifically, we propose that the lysosomotropic effects of hydroxychloroquine and several other drugs undergoing testing may be responsible for their demonstrated in vitro antiviral activities against COVID-19. Moreover, we propose that Niemann-Pick disease type C (NPC), a lysosomal storage disorder, may provide new insights into potential future therapeutic targets for SARS-CoV-2, by highlighting key established features of the disorder that together result in an "unfavorable" host cellular environment that may interfere with viral propagation. Our reasoning evolves from previous biochemical and cell biology findings related to NPC, coupled with the rapidly evolving data on COVID-19. Our overall aim is to suggest that pharmacological interventions targeting lysosomal function in general, and those particularly capable of reversibly inducing transient NPC-like cellular and biochemical phenotypes, constitute plausible mechanisms that could be used to therapeutically target COVID-19.