氯喹和羟氯喹抗病毒机制的图解说明

川普总统推荐了氯喹治疗COVID-19，但有很多人质疑这是不是一种大力丸。其实，武汉病毒所很早就用实验表明氯喹在体外抑制新冠病毒的效力与瑞德西韦相仿。最近一篇文章总结了氯喹和羟氯喹的抗新冠病毒的作用机制(下图)。这些机制提示，氯喹和羟氯喹不仅阻断冠状病毒的侵袭和复制，而且降低了发生细胞因子风暴的可能性。中国（氯喹）和法国（羟氯喹）的临床试验表明氯喹和羟氯喹可以有效抗击COVID-19。因此，氯喹和羟氯喹虽然便宜，也非特效神药，但的确不是大力丸。

相比而言羟氯喹的副作用小，相对安全，是否羟氯喹的效果低于氯喹，还有待试验证明。两者长期大剂量使用都有安全问题，使用时一定要遵从医嘱。

下文及图来自文献(详见后)，供有疑问的朋友参考。

【1】二者均可干扰ACE2的糖基化，并降低宿主细胞上ACE2与冠状病毒表面上的棘突蛋白之间的结合效率。

【2】它们还可以提高内体和溶酶体的pH，从而防止病毒与宿主细胞融合以及随后的复制。

【3】羟氯喹进入抗原呈现细胞时，会阻止抗原加工和主要组织相容性复合体II类介导的自身抗原呈现给T细胞。随后抑制了T细胞的活化以及CD154和其他细胞因子的表达。

【4】羟氯喹破坏了DNA / RNA与TLR和核酸感受器环GMP合成酶(cGAS）的相互作用，因此激促炎基因的转录不能得到激发。

根据上述机制，氯喹和羟氯喹不仅阻断冠状病毒的侵袭和复制，而且降低发生细胞因子风暴的可能性。

Graphical illustration of the antiviral mechanisms of CQ and HCQ. Both chemicals can interfere with the glycosylation of ACE2 and reduce the binding efficiency between ACE2 on the host cells and the spike protein on the surface of the coronavirus. They can also increase the pH of endosomes and lysosomes, through which the fusion process of the virus with host cells and subsequent replication are prevented. When HCQ enters APCs, it prevents antigen processing and MHC class II-mediated autoantigen presentation to T cells. The subsequent activation of T cells and expression of CD154 and other cytokines are repressed. In addition, HCQ disrupts the interaction of DNA/RNA with TLRs and the nucleic acid sensor cGAS and therefore the transcription of pro-inflammatory genes cannot be stimulated. As a result, administration of CQ or HCQ not only blocks the invasion and replication of coronavirus, but also attenuates the possibility of cytokine storm. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.

 

参考文献：

Dan Zhou, Sheng-Ming Dai, Qiang Tong. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. Journal of Antimicrobial Chemotherapy, dkaa114, https://doi.org/10.1093/jac/dkaa114

Published: 20 March 2020

https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkaa114/5810487