In vitro evaluation of antiviral activity of single and combined repurposable drugs against SARS-CoV-2
In vitro evaluation of antiviral activity of single and combined repurposable drugs against SARS-CoV-2
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DOI：
10.1016/j.antiviral.2020.104878
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发表时间：
2020-09-01
影响因子：
7.6
通讯作者：
Terrier, Olivier
中科院分区：
文献类型：
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作者：
Pizzorno, Andres;Padey, Blandine;Terrier, Olivier
为了应对目前由新型SARS-CoV-2引起的大流行，识别和验证有效的治疗策略比以往任何时候都更有必要。我们评估了一系列化合物的体外抗病毒活性，这些化合物以其细胞广谱活性而闻名，以及目前正在COVID-19患者临床试验中评估的药物。我们报告了Remdesivir、lopinavir、chloroquine、umifenovir、berberine和cyclosporine A在SARS-CoV-2感染的Vero E6细胞模型中的抗病毒作用，估计的50%抑制浓度分别为0.99、5.2、1.38、3.5、10.6和3 μ M。还研究了病毒定向加宿主定向的药物组合。我们报告了一个强烈的拮抗作用之间的remdesivir和黄连素，与remdesivir/地尔硫卓，我们描述了高水平的协同作用，平均Loewe协同得分为12和峰值以上50。针对宿主的药物与直接作用的抗病毒药物的组合强调了在更多生理模型中的进一步验证，但它们为COVID-19的治疗开辟了有趣的途径。
In response to the current pandemic caused by the novel SARS-CoV-2, identifying and validating effective therapeutic strategies is more than ever necessary. We evaluated the in vitro antiviral activities of a shortlist of compounds, known for their cellular broad-spectrum activities, together with drugs that are currently under evaluation in clinical trials for COVID-19 patients. We report the antiviral effect of remdesivir, lopinavir, chloroquine, umifenovir, berberine and cyclosporine A in Vero E6 cells model of SARS-CoV-2 infection, with estimated 50% inhibitory concentrations of 0.99, 5.2, 1.38, 3.5, 10.6 and 3 mu M, respectively. Virus-directed plus host-directed drug combinations were also investigated. We report a strong antagonism between remdesivir and berberine, in contrast with remdesivir/diltiazem, for which we describe high levels of synergy, with mean Loewe synergy scores of 12 and peak values above 50. Combination of host-directed drugs with direct acting antivirals underscore further validation in more physiological models, yet they open up interesting avenues for the treatment of COVID-19.