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关于氯喹/羟氯喹可能作用模式的综述:重新用于对抗 SAR-CoV-2(COVID-19)大流行。

A review on possible modes of action of chloroquine/hydroxychloroquine: repurposing against SAR-CoV-2 (COVID-19) pandemic.

机构信息

Department of Pharmacology, School of Medicine, Faculty of Health Sciences, University of the Free State, Bloemfontein 9300, South Africa.

Ex-Professor, Department of Human Physiology with Community Health, Vidyasagar University, Paschim Medinipur 721102, India.

出版信息

Int J Antimicrob Agents. 2020 Aug;56(2):106028. doi: 10.1016/j.ijantimicag.2020.106028. Epub 2020 May 22.

Abstract

Chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) have long been used worldwide as frontline drugs for the treatment and prophylaxis of human malaria. Since the first reported cases in Wuhan, China, in late December 2019, humans have been under threat from coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 (previously known as 2019-nCoV), subsequently declared a pandemic. While the world is searching for expedited approval for a vaccine, which may be only preventative and not a cure, physicians and country leaders are considering several concerted clinical trials suggesting that the age-old antimalarial drugs CQ/HCQ could be a potent therapeutic against COVID-19. Based on accumulating scientific reports, here we highlight the possible modes of action of CQ/HCQ that could justify its use against viral infections. Considering the global health crisis of the COVID-19 pandemic, the option of repurposing old drugs, e.g. CQ/HCQ, particularly HCQ, for the treatment of SARS-CoV-2 infection could be a good choice. CQ/HCQ has diverse modes of action, including alteration of the acidic environment inside lysosomes and late endosomes, preventing endocytosis, exosome release and phagolysosomal fusion, and inhibition of the host cytokine storm. One or more diverse mechanisms might work against viral infections and reduce mortality. As there is no cure for COVID-19, clinical testing of HCQ is urgently required to determine its potency against SARS-CoV-2, as this is the currently available treatment option. There remains a need to find other innovative drug candidates as possible candidates to enter clinical evaluation and testing.

摘要

氯喹(CQ)及其类似物羟氯喹(HCQ)长期以来一直被全球用作治疗和预防人类疟疾的一线药物。自 2019 年 12 月下旬中国武汉首次报告病例以来,人类一直受到新型冠状病毒 SARS-CoV-2(以前称为 2019-nCoV)引起的 2019 冠状病毒病(COVID-19)的威胁,随后该病毒被宣布为大流行。虽然世界正在寻找加快批准疫苗的方法,但疫苗可能只是预防性的,而不是治疗性的,但医生和国家领导人正在考虑几项协同临床试验,表明古老的抗疟药物 CQ/HCQ 可能是对抗 COVID-19 的有效治疗方法。基于不断积累的科学报告,在这里我们强调了 CQ/HCQ 可能对抗病毒感染的作用模式。考虑到 COVID-19 大流行这一全球健康危机,重新利用旧药物(例如 CQ/HCQ,尤其是 HCQ)治疗 SARS-CoV-2 感染的选择可能是一个不错的选择。CQ/HCQ 具有多种作用模式,包括改变溶酶体和晚期内体的酸性环境,阻止内吞作用、外泌体释放和吞噬溶酶体融合,以及抑制宿主细胞因子风暴。一种或多种不同的机制可能对病毒感染有效,并降低死亡率。由于目前还没有治疗 COVID-19 的方法,因此迫切需要对 HCQ 进行临床测试,以确定其对 SARS-CoV-2 的疗效,因为这是目前可用的治疗选择。仍需要寻找其他创新药物候选物作为可能进入临床评估和测试的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a02/7243790/9661f8c77e88/gr1_lrg.jpg

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