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 Glee...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.Anα-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.展开更多
基金We thank LetPub for its linguistic assistance during the preparation of this manuscriptThis work was supported by the National Natural Science Foundation of China(31300207)+1 种基金the Preeminent Youth Fund of Sichuan Province(2015JQO045)the Support Program of Sichuan Agricultural University(03570305).
文摘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.Anα-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.
