Identification of 53 compounds that block Ebola virus-like particle entry via a repurposing screen of approved drugs.
Identification of 53 compounds that block Ebola virus-like particle entry via a repurposing screen of approved drugs.
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DOI：
10.1038/emi.2014.88
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发表时间：
2014-12
影响因子：
13.2
通讯作者：
Garcia-Sastre, Adolfo
中科院分区：
文献类型：
--
作者：
Kouznetsova, Jennifer;Sun, Wei;Martinez-Romero, Carles;Tawa, Gregory;Shinn, Paul;Chen, Catherine Z.;Schimmer, Aaron;Sanderson, Philip;McKew, John C.;Zheng, Wei;Garcia-Sastre, Adolfo
关键词：
鉴于当前埃博拉病毒病的爆发，迫切需要开发有效的疗法来治疗埃博拉感染，而药物再利用筛选是识别此类疗法的潜在快速方法。我们开发了一种生物安全 2 级 (BSL-2) 1536 孔板测定法，用于筛选含有糖蛋白 (GP) 和与 β-内酰胺酶报告蛋白融合的基质 VP40 蛋白的埃博拉病毒样颗粒 (VLP) 的进入抑制剂，并将该测定法应用于食品和药物管理局 (FDA) 批准的药物的快速药物再利用筛选。我们在此报告了 53 种具有阻断埃博拉 VLP 进入细胞活性的药物的鉴定。这53种活性化合物可分为微管抑制剂、雌激素受体调节剂、抗组胺药、抗精神病药、泵/通道拮抗剂和抗癌/抗生素等类别。其中几种化合物，包括微管抑制剂和雌激素受体调节剂，此前曾被报道在 BSL-4 感染性埃博拉病毒复制测定和动物模型研究中具有活性。我们的测定代表了一种稳健、有效和快速的高通量筛选，用于鉴定治疗埃博拉病毒感染的药物开发中的先导化合物。
In light of the current outbreak of Ebola virus disease, there is an urgent need to develop effective therapeutics to treat Ebola infection, and drug repurposing screening is a potentially rapid approach for identifying such therapeutics. We developed a biosafety level 2 (BSL-2) 1536-well plate assay to screen for entry inhibitors of Ebola virus-like particles (VLPs) containing the glycoprotein (GP) and the matrix VP40 protein fused to a beta-lactamase reporter protein and applied this assay for a rapid drug repurposing screen of Food and Drug Administration (FDA)-approved drugs. We report here the identification of 53 drugs with activity of blocking Ebola VLP entry into cells. These 53 active compounds can be divided into categories including microtubule inhibitors, estrogen receptor modulators, antihistamines, antipsychotics, pump/channel antagonists, and anticancer/antibiotics. Several of these compounds, including microtubule inhibitors and estrogen receptor modulators, had previously been reported to be active in BSL-4 infectious Ebola virus replication assays and in animal model studies. Our assay represents a robust, effective and rapid high-throughput screen for the identification of lead compounds in drug development for the treatment of Ebola virus infection.
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DOI：
10.1056/nejmoa1411100
发表时间：
2014-10-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
WHO Ebola Response Team;Aylward B;Barboza P;Bawo L;Bertherat E;Bilivogui P;Blake I;Brennan R;Briand S;Chakauya JM;Chitala K;Conteh RM;Cori A;Croisier A;Dangou JM;Diallo B;Donnelly CA;Dye C;Eckmanns T;Ferguson NM;Formenty P;Fuhrer C;Fukuda K;Garske T;Gasasira A;Gbanyan S;Graaff P;Heleze E;Jambai A;Jombart T;Kasolo F;Kadiobo AM;Keita S;Kertesz D;Koné M;Lane C;Markoff J;Massaquoi M;Mills H;Mulba JM;Musa E;Myhre J;Nasidi A;Nilles E;Nouvellet P;Nshimirimana D;Nuttall I;Nyenswah T;Olu O;Pendergast S;Perea W;Polonsky J;Riley S;Ronveaux O;Sakoba K;Santhana Gopala Krishnan R;Senga M;Shuaib F;Van Kerkhove MD;Vaz R;Wijekoon Kannangarage N;Yoti Z
通讯作者：
Yoti Z
DOI：
10.2174/1875397301004010057
发表时间：
2010-10-21
期刊：
Current chemical genomics
影响因子：
--
作者：
Wang Y;Jadhav A;Southal N;Huang R;Nguyen DT
通讯作者：
Nguyen DT
影响因子：
3.6
作者：
Xia M;Huang R;Sakamuru S;Alcorta D;Cho MH;Lee DH;Park DM;Kelley MJ;Sommer J;Austin CP
通讯作者：
Austin CP
影响因子：
17.1
作者：
Johansen LM;Brannan JM;Delos SE;Shoemaker CJ;Stossel A;Lear C;Hoffstrom BG;Dewald LE;Schornberg KL;Scully C;Lehár J;Hensley LE;White JM;Olinger GG
通讯作者：
Olinger GG
影响因子：
8
作者：
Jang, ER;Lim, SJ;Lee, JS
通讯作者：
Lee, JS