Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro

Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro
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DOI:
10.1016/j.antiviral.2020.104786
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发表时间:
2020-06-01
期刊:
影响因子:
7.6
通讯作者:
Yen, Hui-Ling
Yen, Hui-Ling
中科院分区:
医学2区
文献类型:
--
作者:
Choy, Ka-Tim;Wong, Alvina Yin-Lam;Yen, Hui-Ling

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由新型SARS-CoV-2病毒引起的不断升级的大流行正在影响全球健康,迫切需要有效的治疗方案。我们评估了先前报道的抑制冠状病毒复制的化合物和目前正在对SARS-CoV-2患者进行临床试验评估的化合物的体外抗病毒作用。我们在Vero E6细胞中报道了瑞德西韦、洛匹那韦、同丁胺和艾美汀对SARS-CoV-2病毒的抗病毒作用,估计50%的有效浓度分别为23.15 μ M、26.63 μ M、2.55 μ M和0.46 μ M。目前正在临床试验中评估的利巴韦林或法匹拉韦在100 μ M时没有抑制作用,观察到瑞德西韦与艾美汀的协同作用,6.25 μ M的瑞德西韦与0.195 μ M的艾美汀联合使用,可实现64.9%的病毒产量抑制。联合治疗可能有助于将化合物的有效浓度降低到治疗血浆浓度以下,并提供更好的临床效益。
An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 mu M, 26.63 mu M, 2.55 mu M and 0.46 mu M, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 mu M. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 mu M in combination with emetine at 0.195 mu M may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.