Unité Parasitologie et Entomologie, Département Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, Marseille, France; Aix-Marseille Université, IRD, SSA, AP-HM, VITROME, Marseille, France; IHU Méditerranée Infection, Marseille, France.
IHU Méditerranée Infection, Marseille, France; Aix-Marseille Université, IRD, AP-HM, MEPHI, Marseille, France.
Int J Antimicrob Agents. 2020 Dec;56(6):106202. doi: 10.1016/j.ijantimicag.2020.106202. Epub 2020 Oct 16.
In December 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus diseases 2019 (COVID-19) emerged in Wuhan, China. Currently there is no antiviral treatment recommended against SARS-CoV-2. Identifying effective antiviral drugs is urgently required. Methylene blue has already demonstrated in vitro antiviral activity in photodynamic therapy as well as antibacterial, antifungal and antiparasitic activities in non-photodynamic assays. In this study. non-photoactivated methylene blue showed in vitro activity at very low micromolar range with an EC (median effective concentration) of 0.30 ± 0.03 μM and an EC (90% effective concentration) of 0.75 ± 0.21 μM at a multiplicity of infection (MOI) of 0.25 against SARS-CoV-2 (strain IHUMI-3). The EC and EC values for methylene blue are lower than those obtained for hydroxychloroquine (1.5 μM and 3.0 μM) and azithromycin (20.1 μM and 41.9 μM). The ratios C/EC and C/EC in blood for methylene blue were estimated at 10.1 and 4.0, respectively, following oral administration and 33.3 and 13.3 following intravenous administration. Methylene blue EC and EC values are consistent with concentrations observed in human blood. We propose that methylene blue is a promising drug for treatment of COVID-19. In vivo evaluation in animal experimental models is now required to confirm its antiviral effects on SARS-CoV-2. The potential interest of methylene blue to treat COVID-19 needs to be confirmed by prospective comparative clinical studies.
2019 年 12 月，一种新型冠状病毒，严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）在中国武汉引发了 2019 年冠状病毒病（COVID-19）。目前尚无针对 SARS-CoV-2 的推荐抗病毒治疗方法。迫切需要确定有效的抗病毒药物。亚甲蓝在光动力疗法中已显示出体外抗病毒活性，在非光动力测定中也具有抗菌、抗真菌和抗寄生虫活性。在这项研究中，非光活化亚甲蓝在非常低的微摩尔范围内表现出体外活性，在感染复数（MOI）为 0.25 时，对 SARS-CoV-2（IHUMI-3 株）的 EC（半数有效浓度）为 0.30±0.03 μM，EC（90%有效浓度）为 0.75±0.21 μM。亚甲蓝的 EC 和 EC 值均低于羟氯喹（1.5 μM 和 3.0 μM）和阿奇霉素（20.1 μM 和 41.9 μM）。口服后，亚甲蓝在血液中的 C/EC 和 C/EC 比值分别估计为 10.1 和 4.0，静脉注射后分别为 33.3 和 13.3。亚甲蓝的 EC 和 EC 值与人类血液中观察到的浓度一致。我们提出亚甲蓝是治疗 COVID-19 的一种很有前途的药物。现在需要在动物实验模型中进行体内评估以确认其对 SARS-CoV-2 的抗病毒作用。需要前瞻性比较临床研究来证实亚甲蓝治疗 COVID-19 的潜在益处。
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