氯喹和羥氯喹抗病毒機製的圖解說明

川普總統推薦了氯喹治療COVID-19，但有很多人質疑這是不是一種大力丸。其實，武漢病毒所很早就用實驗表明氯喹在體外抑製新冠病毒的效力與瑞德西韋相仿。最近一篇文章總結了氯喹和羥氯喹的抗新冠病毒的作用機製(下圖)。這些機製提示，氯喹和羥氯喹不僅阻斷冠狀病毒的侵襲和複製，而且降低了發生細胞因子風暴的可能性。中國（氯喹）和法國（羥氯喹）的臨床試驗表明氯喹和羥氯喹可以有效抗擊COVID-19。因此，氯喹和羥氯喹雖然便宜，也非特效神藥，但的確不是大力丸。

相比而言羥氯喹的副作用小，相對安全，是否羥氯喹的效果低於氯喹，還有待試驗證明。兩者長期大劑量使用都有安全問題，使用時一定要遵從醫囑。

下文及圖來自文獻(詳見後)，供有疑問的朋友參考。

【1】二者均可幹擾ACE2的糖基化，並降低宿主細胞上ACE2與冠狀病毒表麵上的棘突蛋白之間的結合效率。

【2】它們還可以提高內體和溶酶體的pH，從而防止病毒與宿主細胞融合以及隨後的複製。

【3】羥氯喹進入抗原呈現細胞時，會阻止抗原加工和主要組織相容性複合體II類介導的自身抗原呈現給T細胞。隨後抑製了T細胞的活化以及CD154和其他細胞因子的表達。

【4】羥氯喹破壞了DNA / RNA與TLR和核酸感受器環GMP合成酶(cGAS）的相互作用，因此激促炎基因的轉錄不能得到激發。

根據上述機製，氯喹和羥氯喹不僅阻斷冠狀病毒的侵襲和複製，而且降低發生細胞因子風暴的可能性。

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.

 

參考文獻：

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