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羟氯喹在非人类灵长类动物中对抗 SARS-CoV-2 感染的应用。

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

机构信息

Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.

Université de Paris, IAME, Inserm, Paris, France.

出版信息

Nature. 2020 Sep;585(7826):584-587. doi: 10.1038/s41586-020-2558-4. Epub 2020 Jul 22.

Abstract

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. 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. 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.

摘要

2019 年冠状病毒病(COVID-19)迅速成为全球性大流行疾病,目前尚无治疗该病的抗病毒药物或疫苗。正在进行几项临床研究,以评估已证明具有体外抗病毒功效的药物的功效。在这些候选药物中,羟氯喹(HCQ)已在全球范围内用于数千名感染严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)的个体,该病毒是引起 COVID-19 的病毒,但尚无明确证据表明 HCQ 对治疗 COVID-19 有效。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 在非洲绿猴肾细胞(Vero E6)中具有抗病毒活性,但在重建的人呼吸道上皮模型中没有活性。在猕猴中,我们在病毒载量达到峰值之前和之后,单独或与阿奇霉素(AZTH)联合,测试了与安慰剂治疗相比的不同治疗策略。在任何分析的组织中,HCQ 或 HCQ 与 AZTH 的联合均未显示对病毒载量有明显影响。当将该药物用作暴露前预防治疗时,HCQ 不能预防感染 SARS-CoV-2。我们的研究结果不支持将 HCQ 单独或与 AZTH 联合用作治疗人类 COVID-19 的抗病毒药物。

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