Synergistic and Antagonistic Drug Combinations against SARS-CoV-2.
Synergistic and Antagonistic Drug Combinations against SARS-CoV-2.
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DOI：
10.1016/j.ymthe.2020.12.016
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发表时间：
2021-02-03
期刊：
影响因子：
--
通讯作者：
Muratov EN
中科院分区：
文献类型：
--
作者：
Bobrowski T;Chen L;Eastman RT;Itkin Z;Shinn P;Chen CZ;Guo H;Zheng W;Michael S;Simeonov A;Hall MD;Zakharov AV;Muratov EN
针对2019冠状病毒病（COVID-19）的抗病毒药物开发正在以前所未有的速度进行，但治疗这种疾病的治疗选择仍然有限。我们假设联合具有独立作用机制的药物可产生协同作用，从而产生更好的抗病毒效果。利用计算机方法，我们对32种具有潜在抗SARS-CoV-2活性的药物的73种组合进行了优先排序，然后在体外进行了测试。鉴定出16种协同组合和8种拮抗组合；在16例协同作用病例中，美国食品和药物管理局（FDA）批准的药物硝唑昔尼特与瑞德西韦、阿莫地喹或乌米诺韦联合使用最为显著，在细胞模型中均表现出对SARS-CoV-2的显著协同作用。然而，瑞德西韦与羟氯喹等促溶体药物联合使用，表现出强烈的拮抗作用。总的来说，这些结果突出了药物再利用和药物组合临床前测试在发现治疗COVID-19的潜在疗法方面的作用。在计算机上鉴定了16种抗SARS-CoV-2的协同药物组合，并进行了实验验证。硝唑昔尼特与瑞德西韦、阿莫地喹或乌米诺韦联合使用对SARS-CoV-2表现出显著的协同作用。雷德西韦与羟氯喹或其他溶酶体药物合用可产生强烈的拮抗作用。
Antiviral drug development for coronavirus disease 2019 (COVID-19) is occurring at an unprecedented pace, yet there are still limited therapeutic options for treating this disease. We hypothesized that combining drugs with independent mechanisms of action could result in synergy against SARS-CoV-2, thus generating better antiviral efficacy. Using in silico approaches, we prioritized 73 combinations of 32 drugs with potential activity against SARS-CoV-2 and then tested them in vitro. Sixteen synergistic and eight antagonistic combinations were identified; among 16 synergistic cases, combinations of the US Food and Drug Administration (FDA)-approved drug nitazoxanide with remdesivir, amodiaquine, or umifenovir were most notable, all exhibiting significant synergy against SARS-CoV-2 in a cell model. However, the combination of remdesivir and lysosomotropic drugs, such as hydroxychloroquine, demonstrated strong antagonism. Overall, these results highlight the utility of drug repurposing and preclinical testing of drug combinations for discovering potential therapies to treat COVID-19. Sixteen synergistic drug combinations against SARS-CoV-2 were identified in silico and confirmed experimentally. Combinations of nitazoxanide with remdesivir, amodiaquine, or umifenovir exhibited significant synergy against SARS-CoV-2. Remdesivir combined with hydroxychloroquine or other lysosomotropic drugs resulted in strong antagonism.
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DOI：
10.1086/653080
发表时间：
2010-07-01
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Einav S;Sobol HD;Gehrig E;Glenn JS
通讯作者：
Glenn JS
影响因子：
5.6
作者：
Bizon, Chris;Cox, Steven;Tropsha, Alexander
通讯作者：
Tropsha, Alexander
DOI：
10.1099/jgv.0.001481
发表时间：
2020-11
期刊：
The Journal of general virology
影响因子：
--
作者：
Klimstra WB;Tilston-Lunel NL;Nambulli S;Boslett J;McMillen CM;Gilliland T;Dunn MD;Sun C;Wheeler SE;Wells A;Hartman AL;McElroy AK;Reed DS;Rennick LJ;Duprex WP
通讯作者：
Duprex WP
DOI：
10.1111/cts.12592
发表时间：
2019-03
期刊：
Clinical and translational science
影响因子：
--
作者：
Biomedical Data Translator Consortium
通讯作者：
Biomedical Data Translator Consortium
影响因子：
5.6
作者：
Fourches D;Muratov E;Tropsha A
通讯作者：
Tropsha A