Antimalarial artemisinin-based combination therapies (ACT) and COVID-19 in Africa: In vitro inhibition of SARS-CoV-2 replication by mefloquine-artesunate
Antimalarial artemisinin-based combination therapies (ACT) and COVID-19 in Africa: In vitro inhibition of SARS-CoV-2 replication by mefloquine-artesunate
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DOI：
10.1016/j.ijid.2020.08.032
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发表时间：
2020-10-01
影响因子：
8.4
通讯作者：
Pradines, Bruno
中科院分区：
文献类型：
--
作者：
Gendrot, Mathieu;Duflot, Isabelle;Pradines, Bruno
目的：2019年11月底，中国出现了一种导致呼吸道感染的新型冠状病毒（COVID-19）。尽管采取了严厉的遏制措施，这种被称为严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）的病毒仍在亚洲和欧洲蔓延。这种流行病正在南欧和美洲的一个特定热点地区持续蔓延;许多研究预测非洲也会出现类似的流行病，就像目前在欧洲和美利坚合众国看到的那样。然而，报告的数据并没有证实这些预测。可以解释COVID-19大流行后来在非洲国家出现和传播的假设之一是使用抗疟药物治疗疟疾，特别是青蒿素联合疗法（ACT）。方法：在体外评价了固定浓度ACT的抗病毒活性，其浓度与口服ACT治疗无并发症疟疾时在人血浆中观察到的浓度一致结果：甲氟喹-青蒿琥酯在治疗疟疾的常用剂量下对SARS-CoV-2临床分离株（IHUMI-3）具有最高的抗病毒活性，抑制率为72.1 ± 18.3%。所有其他的组合，青蒿琥酯阿莫地喹，蒿甲醚，苯芴醇，青蒿琥酯，咯萘啶，或双氢青蒿素，哌喹，显示在相同的范围内的抗病毒抑制（27.1至34.1%）。结论：抗疟药物的浓度数据，在肺中是可用的集中从10到160倍以上，在肺比在血液中。这些体外结果强化了抗疟疾药物可能有效作为抗COVID-19治疗的假设。(C)2020作者（S）由爱思唯尔有限公司代表国际传染病学会出版。
Objectives: At the end of November 2019, a novel coronavirus responsible for respiratory tract infections (COVID-19) emerged in China. Despitedrastic containment measures,this virus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread in Asia and Europe. The pandemic is ongoing with a particular hotspot in Southern Europe and America; many studies predicted a similar epidemic in Africa, as is currently seen in Europe and the United States of America. However, reported data have not confirmed these predictions. One of the hypotheses that could explain the later emergence and spread of COVID-19 pandemic in African countries is the use of antimalarial drugs to treat malaria, and specifically, artemisinin-based combination therapy (ACT).Methods: The antiviral activity of fixed concentrations of ACT at concentrations consistent with those observed in human plasma when ACT is administered at oral doses for uncomplicated malaria treatment was evaluated in vitro against a clinically isolated SARS-CoV-2 strain (IHUMI-3) in Vero E6 cells.Results: Mefloquine-artesunate exerted the highest antiviral activity with% inhibition of 72.1 +/- 18.3% atexpected maximum blood concentration (C-max) for each ACT drug at doses commonly administered in malaria treatment. All the other combinations, artesunate-amodiaquine, artemether-lumefantrine, artesunate-pyronaridine, or dihydroartemisinin-piperaquine, showed antiviral inhibition in the same ranges (27.1 to 34.1 %).Conclusions: Antimalarial drugs for which concentration data in the lungs are available are concentrated from 10 to 160 fold more in the lungs than in blood. These in vitro results reinforce the hypothesis that antimalarial drugs could be effective as an anti-COVID-19 treatment. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.