Berberine and Obatoclax Inhibit SARS-Cov-2 Replication in Primary Human Nasal Epithelial Cells In Vitro.
Berberine and Obatoclax Inhibit SARS-Cov-2 Replication in Primary Human Nasal Epithelial Cells In Vitro.
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DOI：
10.3390/v13020282
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发表时间：
2021-02-11
期刊：
影响因子：
--
通讯作者：
van Rij RP
中科院分区：
文献类型：
--
作者：
Varghese FS;van Woudenbergh E;Overheul GJ;Eleveld MJ;Kurver L;van Heerbeek N;van Laarhoven A;Miesen P;den Hartog G;de Jonge MI;van Rij RP
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）于2019年底作为一种新的人类病原体出现，在不到一年的时间里感染了超过1亿人。显然需要有效的抗病毒药物来补充目前的预防措施，包括疫苗。在这项研究中，我们证明，小檗碱和obatoclax，两个广谱抗病毒化合物，是有效的对多个分离的SARS-CoV-2。小檗碱是一种植物衍生的生物碱，在低微摩尔浓度下抑制SARS-CoV-2，而最初作为抗凋亡蛋白拮抗剂开发的obatoclax在亚微摩尔浓度下有效。添加时间研究表明，小檗碱作用于病毒生命周期的后期阶段。与此一致，小檗碱轻度影响病毒RNA合成，但它强烈降低感染性病毒滴度，导致颗粒与pfu比率增加。相比之下，obatoclax在感染的早期阶段起作用，这与其中和内体中酸性环境的活性一致。我们评估了在空气-液体界面上培养的原代人鼻上皮细胞的感染，发现SARS-CoV-2感染诱导并抑制了特定细胞因子和趋化因子的表达。此外，obatoclax和小檗碱抑制SARS-CoV-2在这些主要靶细胞中的复制。我们建议黄连素和obatoclax作为潜在的抗SARS-CoV-2的抗病毒药物，可以考虑进行进一步的疗效测试。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a new human pathogen in late 2019 and it has infected over 100 million people in less than a year. There is a clear need for effective antiviral drugs to complement current preventive measures, including vaccines. In this study, we demonstrate that berberine and obatoclax, two broad-spectrum antiviral compounds, are effective against multiple isolates of SARS-CoV-2. Berberine, a plant-derived alkaloid, inhibited SARS-CoV-2 at low micromolar concentrations and obatoclax, which was originally developed as an anti-apoptotic protein antagonist, was effective at sub-micromolar concentrations. Time-of-addition studies indicated that berberine acts on the late stage of the viral life cycle. In agreement, berberine mildly affected viral RNA synthesis, but it strongly reduced infectious viral titers, leading to an increase in the particle-to-pfu ratio. In contrast, obatoclax acted at the early stage of the infection, which is in line with its activity to neutralize the acidic environment in endosomes. We assessed infection of primary human nasal epithelial cells that were cultured on an air-liquid interface and found that SARS-CoV-2 infection induced and repressed expression of specific sets of cytokines and chemokines. Moreover, both obatoclax and berberine inhibited SARS-CoV-2 replication in these primary target cells. We propose berberine and obatoclax as potential antiviral drugs against SARS-CoV-2 that could be considered for further efficacy testing.
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DOI：
10.1056/nejmoa2022926
发表时间：
2020-11-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
RECOVERY Collaborative Group;Horby P;Mafham M;Linsell L;Bell JL;Staplin N;Emberson JR;Wiselka M;Ustianowski A;Elmahi E;Prudon B;Whitehouse T;Felton T;Williams J;Faccenda J;Underwood J;Baillie JK;Chappell LC;Faust SN;Jaki T;Jeffery K;Lim WS;Montgomery A;Rowan K;Tarning J;Watson JA;White NJ;Juszczak E;Haynes R;Landray MJ
通讯作者：
Landray MJ
DOI：
10.1038/nrmicro.2016.81
发表时间：
2016-08
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
de Wit E;van Doremalen N;Falzarano D;Munster VJ
通讯作者：
Munster VJ
影响因子：
5
作者：
Gorbalenya AE;Enjuanes L;Ziebuhr J;Snijder EJ
通讯作者：
Snijder EJ
影响因子：
4.7
作者：
Ianevski, Aleksandr;Yao, Rouan;Kainov, Denis E.
通讯作者：
Kainov, Denis E.
影响因子：
64.8
作者：
Hoffmann, Markus;Moesbauer, Kirstin;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan