University Department of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili di Brescia, Brescia, Italy.
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy; Clinical Chemistry Laboratory, Cytogenetics and Molecular Genetics Section, Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy.
Pharmacol Res. 2020 Aug;158:104904. doi: 10.1016/j.phrs.2020.104904. Epub 2020 May 13.
The anti-malarial drugs chloroquine (CQ) and primarily the less toxic hydroxychloroquine (HCQ) are currently used to treat autoimmune diseases for their immunomodulatory and anti-thrombotic properties. They have also been proposed for the treatment of several viral infections, due to their anti-viral effects in cell cultures and animal models, and, currently, for the treatment of coronavirus disease 2019 (COVID-19), the pandemic severe acute respiratory syndrome caused by coronavirus 2 (Sars-Cov-2) infection that is spreading all over the world. Although in some recent studies a clinical improvement in COVID-19 patients has been observed, the clinical efficacy of CQ and HCQ in COVID-19 has yet to be proven with randomized controlled studies, many of which are currently ongoing, also considering pharmacokinetics, optimal dosing regimen, therapeutic level and duration of treatment and taking into account patients with different severity degrees of disease. Here we review what is currently known on the mechanisms of action of CQ and HCQ as anti-viral, anti-inflammatory and anti-thrombotic drugs and discuss the up-to-date experimental evidence on the potential mechanisms of action of CQ/HCQ in Sars-Cov2 infection and the current clinical knowledge on their efficacy in the treatment of COVID-19 patients. Given the role of iron in several human viral infections, we also propose a different insight into a number of CQ and HCQ pharmacological effects, suggesting a potential involvement of iron homeostasis in Sars-Cov-2 infection and COVID-19 clinical course.
抗疟药氯喹（CQ）和主要的毒性较低的羟氯喹（HCQ）目前用于治疗自身免疫性疾病，因为它们具有免疫调节和抗血栓形成的特性。由于它们在细胞培养物和动物模型中的抗病毒作用，它们也被提议用于治疗几种病毒感染，并且目前还用于治疗 2019 年冠状病毒病（COVID-19），即由冠状病毒 2（Sars-Cov-2）感染引起的全球流行的严重急性呼吸系统综合征。尽管在最近的一些研究中观察到 COVID-19 患者的临床改善，但 CQ 和 HCQ 在 COVID-19 中的临床疗效尚未通过随机对照研究得到证实，目前正在进行许多此类研究，同时还考虑了药代动力学、最佳剂量方案、治疗水平和治疗持续时间，并考虑了疾病严重程度不同的患者。在这里，我们回顾了 CQ 和 HCQ 作为抗病毒、抗炎和抗血栓形成药物的作用机制的最新知识，并讨论了 CQ/HCQ 在 Sars-Cov2 感染中的潜在作用机制的最新实验证据，以及它们在治疗 COVID-19 患者方面的临床疗效。鉴于铁在几种人类病毒感染中的作用，我们还提出了对 CQ 和 HCQ 药理学作用的不同见解，表明铁稳态可能参与了 Sars-Cov-2 感染和 COVID-19 的临床病程。
