Antiviral Screening of Multiple Compounds against Ebola Virus.
Antiviral Screening of Multiple Compounds against Ebola Virus.
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DOI：
10.3390/v8110277
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发表时间：
2016-10-27
期刊：
影响因子：
--
通讯作者：
Carroll MW
中科院分区：
文献类型：
--
作者：
Dowall SD;Bewley K;Watson RJ;Vasan SS;Ghosh C;Konai MM;Gausdal G;Lorens JB;Long J;Barclay W;Garcia-Dorival I;Hiscox J;Bosworth A;Taylor I;Easterbrook L;Pitman J;Summers S;Chan-Pensley J;Funnell S;Vipond J;Charlton S;Haldar J;Hewson R;Carroll MW
鉴于最近在西非爆发埃博拉病毒病，已重新努力寻求有效的抗病毒对策。目前已有一系列具有广泛抗菌活性的化合物对EBOV的活性进行了测试。利用EBOV活体，筛选了18种候选化合物的体外抗病毒活性。这些化合物是在合理的基础上选择的，因为它们的作用机制表明它们有可能破坏EBOV进入、复制或从细胞中退出，或者因为它们在以前的测试中显示出对EBOV的一些抗病毒活性。有9种化合物（齐多夫定、二腺苷、司他夫定、硫酸阿巴卡韦、恩替卡韦、JB1a、Aimspro、celgosivir和castanospermine）在细胞保持健康的情况下没有引起病毒复制的减少，因此它们被排除在进一步的分析之外。对剩余化合物和体内试验可行性的第二次筛选去除了另外六种化合物（瓦巴因、奥美拉唑、埃索美拉唑、格列卫、D-LANA-14和Tasigna）。在EBOV疾病的豚鼠模型中进一步筛选了三种最有希望的化合物（17-DMAG、BGB324和NCK-8）的体内活性。其中两种化合物BGB324和NCK-8在实验浓度下对体内致命感染有一定的抑制作用，值得进一步研究。此外，这些数据增加了多种化合物对埃博拉病毒的抗病毒活性的知识体系，并表明科学界应投入更多精力开发新型和特异性抗病毒化合物来治疗埃博拉病毒病。
In light of the recent outbreak of Ebola virus (EBOV) disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests. Nine compounds caused no reduction in viral replication despite cells remaining healthy, so they were excluded from further analysis (zidovudine; didanosine; stavudine; abacavir sulphate; entecavir; JB1a; Aimspro; celgosivir; and castanospermine). A second screen of the remaining compounds and the feasibility of appropriateness for in vivo testing removed six further compounds (ouabain; omeprazole; esomeprazole; Gleevec; D-LANA-14; and Tasigna). The three most promising compounds (17-DMAG; BGB324; and NCK-8) were further screened for in vivo activity in the guinea pig model of EBOV disease. Two of the compounds, BGB324 and NCK-8, showed some effect against lethal infection in vivo at the concentrations tested, which warrants further investigation. Further, these data add to the body of knowledge on the antiviral activities of multiple compounds against EBOV and indicate that the scientific community should invest more effort into the development of novel and specific antiviral compounds to treat Ebola virus disease.
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影响因子：
3.7
作者：
Ghosh C;Manjunath GB;Konai MM;Uppu DS;Hoque J;Paramanandham K;Shome BR;Haldar J
通讯作者：
Haldar J
DOI：
10.1128/genomea.01178-14
发表时间：
2014-11-01
期刊：
GENOME ANNOUNCEMENTS
影响因子：
--
作者：
Kuhn, Jens H.;Lofts, Loreen L.;Palacios, Gustavo
通讯作者：
Palacios, Gustavo
影响因子：
6.4
作者：
Cross, Robert W.;Fenton, Karla A.;Geisbert, Thomas W.
通讯作者：
Geisbert, Thomas W.
影响因子：
7.6
作者：
Dowall, Stuart;Taylor, Irene;Hewson, Roger
通讯作者：
Hewson, Roger
影响因子：
--
作者：
Fleuren ED;Hillebrandt-Roeffen MH;Flucke UE;Te Loo DM;Boerman OC;van der Graaf WT;Versleijen-Jonkers YM
通讯作者：
Versleijen-Jonkers YM