Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates

Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates
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DOI:
10.1038/s41586-020-2558-4
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发表时间:
2020-07-22
期刊:
影响因子:
64.8
通讯作者:
Le Grand, Roger
Le Grand, Roger
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Maisonnasse, Pauline;Guedj, Jeremie;Le Grand, Roger

文献摘要

被引文献

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羟氯喹不能保护猕猴免受SARS-CoV-2感染或减少感染后的病毒载量;这些发现不支持使用羟氯喹作为人类COVID-19的抗病毒药物治疗。2019冠状病毒病(COVID-19)已迅速成为全球大流行病,目前尚无抗病毒药物或疫苗可用于治疗这种疾病(1-3)。一些临床研究正在进行中,以评估已证明体外抗病毒疗效的再利用药物的疗效。在这些候选药物中,羟氯喹(HCQ)已被用于全球数千名感染严重急性呼吸系统综合征冠状病毒2(SARS-CoV-2)的个体-导致COVID-19的病毒-但没有确切的证据表明HCQ对治疗COVID-19有效(4-7)。在这里,我们评估了HCQ在体外和感染SARS-CoV-2的猕猴中的抗病毒活性。HCQ在非洲绿色猴肾细胞(Vero E6)中显示出抗病毒活性,但在重建的人气道上皮模型中没有。在猕猴中,我们测试了不同的治疗策略,与安慰剂治疗相比,在峰值病毒载量之前和之后,单独或与阿奇霉素(AZTH)联合使用。HCQ或HCQ和AZTH的组合均未显示对任何分析组织中的病毒载量的显著影响。当该药物被用作暴露前预防治疗时,HCQ并没有提供对SARS-CoV-2感染的保护。我们的研究结果不支持使用HCQ,无论是单独使用还是与AZTH联合使用,作为治疗人类COVID-19的抗病毒药物。
Hydroxychloroquine did not confer protection against SARS-CoV-2 infection or reduce the viral load after infection in macaques; these findings do not support the use of hydroxychloroquine as an antiviral drug treatment of COVID-19 in humans.Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic and no antiviral drug or vaccine is yet available for the treatment of this disease(1-3). Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs that have demonstrated antiviral efficacy in vitro. Among these candidates, hydroxychloroquine (HCQ) has been given to thousands of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-the virus that causes COVID-19-worldwide but there is no definitive evidence that HCQ is effective for treating COVID-19(4-7). Here we evaluated the antiviral activity of HCQ both in vitro and in SARS-CoV-2-infected macaques. HCQ showed antiviral activity in African green monkey kidney cells (Vero E6) but not in a model of reconstituted human airway epithelium. In macaques, we tested different treatment strategies in comparison to a placebo treatment, before and after peak viral load, alone or in combination with azithromycin (AZTH). Neither HCQ nor the combination of HCQ and AZTH showed a significant effect on viral load in any of the analysed tissues. When the drug was used as a pre-exposure prophylaxis treatment, HCQ did not confer protection against infection with SARS-CoV-2. Our findings do not support the use of HCQ, either alone or in combination with AZTH, as an antiviral drug for the treatment of COVID-19 in humans.