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

被引:235
作者
Maisonnasse, Pauline [1 ]
Guedj, Jeremie [2 ]
Contreras, Vanessa [1 ]
Behillil, Sylvie [3 ,4 ]
Solas, Caroline [5 ]
Marlin, Romain [1 ]
Naninck, Thibaut [1 ]
Pizzorno, Andres [6 ]
Lemaitre, Julien [1 ]
Goncalves, Antonio [2 ]
Kahlaoui, Nidhal [1 ]
Terrier, Olivier [6 ]
Fang, Raphael Ho Tsong [1 ]
Enouf, Vincent [3 ,4 ,7 ]
Dereuddre-Bosquet, Nathalie [1 ]
Brisebarre, Angela [3 ,4 ]
Touret, Franck [8 ]
Chapon, Catherine [1 ]
Hoen, Bruno [9 ]
Lina, Bruno [6 ,10 ]
Calatrava, Manuel Rosa [6 ]
van der Werf, Sylvie [3 ,4 ]
de Lamballerie, Xavier [8 ]
Le Grand, Roger [1 ]
机构
[1] Univ Paris Saclay, Ctr Immunol Viral, Autoimmune Hematol & Bacterial Dis IMVA HB IDMIT, Inserm,CEA, Fontenay Aux Roses, France
[2] Univ Paris, IAME, INSERM, Paris, France
[3] Univ Paris, CNRS, Inst Pasteur, Unite Genet Mol Virus ARN,GMVR,UMR 3569, Paris, France
[4] Inst Pasteur, Ctr Natl Reference Virus Infect Resp Dont Grippe, Paris, France
[5] Aix Marseille Univ, Lab Pharmacocinet & Toxicol, Hop La Timone,APHM, Unite Virus Emergents UVE IRD 190,INSERM 1207, Marseille, France
[6] Univ Claude Bernard Lyon 1, Univ Lyon, CNRS,INSERM,UMR3508,ENS Lyon, Ctr Int Rech Infectiol,CIRI,U1111,Team VirPath, Lyon, France
[7] Inst Pasteur, Plate Forme Microbiol Mutualisee P2M, Pasteur Int Bioresources Network PIBnet, Paris, France
[8] Aix Marseille Univ, Unite Virus Emergents UVE, IRD 190, INSERM 1207,IHU Mediterranee Infect, Marseille, France
[9] Inst Pasteur, Emerging Dis Epidemiol Unit, Paris, France
[10] Hosp Civils Lyon, Inst Agents Infect, Ctr Natl Reference Virus Infect Resp Dont Grippe, Lab Virol,Grop Hosp Nord, Lyon, France
基金
欧盟地平线“2020”;
关键词
SYSTEMIC-LUPUS-ERYTHEMATOSUS; COVID-19;
D O I
10.1038/s41586-020-2558-4
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:584 / +
页数:15
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