Possible FDA-approved drugs to treat Ebola virus infection

被引:23
|
作者
Yuan, Shu [1 ]
机构
[1] Sichuan Agr Univ, Coll Resources Sci & Technol, Chengdu 611130, Peoples R China
基金
中国国家自然科学基金;
关键词
Ebola virus infection; Disseminated intravascular coagulation; Glycosylation inhibitors; Miglustat; Niemann-Pick C1 inhibitors; Toremifene; ANTIBODY-DEPENDENT ENHANCEMENT; SMALL-MOLECULE INHIBITORS; ER ALPHA-GLUCOSIDASES; POSTEXPOSURE PROTECTION; HEMORRHAGIC-FEVER; NONHUMAN-PRIMATES; CELL; ENTRY; PHARMACOKINETICS; PATHOGENESIS;
D O I
10.1186/s40249-015-0055-z
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
There is currently no effective treatment for the Ebola virus (EBOV) thus far. Most drugs and vaccines developed to date have not yet been approved for human trials. Two FDA-approved c-AbI1 tyrosine kinase inhibitors Gleevec and Tasigna block the release of viral particles; however, their clinical dosages are much lower than the dosages required for effective EBOV suppression. An alpha-1,2-glucosidase inhibitor Miglustat has been shown to inhibit EBOV particle assembly and secretion. Additionally, the estrogen receptor modulators Clomiphene and Toremifene prevent membrane fusion of EBOV and 50-90% of treated mice survived after Clomiphene/Toremifene treatments. However, the uptake efficiency of Clomiphene by oral administration is very low. Thus, I propose a hypothetical treatment protocol to treat Ebola virus infection with a cumulative use of both Miglustat and Toremifene to inhibit the virus effectively and synergistically. EBOV infection induces massive apoptosis of peripheral lymphocytes. Also, cytolysis of endothelial cells triggers disseminated intravascular coagulation (DIC) and subsequent multiple organ failures. Therefore, blood transfusions and active treatments with FDA-approved drugs to treat DIC are also recommended.
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