Repurposing drugs already approved by the FDA for different applications is highly attractive because these drugs have known pharmacology and toxicity profiles, as well as established manufacturing and formulation methods. That’s why thousands of existing drugs, those currently in use, are being screened by pharma companies for efficacy in other diseases of conditions. Some of these results are very surprising. Recently it was found that two known drugs that are already being used for other conditions might offer protection against infection by Ebola Virus. These findings are really significant since there is currently no effective treatment for Ebola infection. Vascor (Bepridil), a calcium channel blocker used to treat angina, and interestingly, Zoloft (Sertraline), a selective serotonin reuptake inhibitor (SSRI) used to treat anxiety and depression, were recently shown to inhibit virus replication in cells in tissue culture, and also to protect mice from virus infection.
First drugs were tested for their ability to prevent the virus from replicating/reproducing in cells in tissue culture. The cells were also tested for viability to make sure the drugs weren’t simply killing the cells. Several known drugs showed anti-virus activity in these experiments. The authors selected drugs with proven track records for safety in man as candidates for further studies. Two of the most promising were Vascor (Bepridil) and Zoloft (Sertraline).
Next, the drugs were tested for their ability protect mice from infection with the virus. One hour after the mice were infected with the virus, drug treatment was started. Drugs were given to the mice for 10 days, and then the mice were observed for another 18 days. Zoloft treatment resulted in 70% survival (7/10) of the infected mice. Vascor (Bepridil) treatment resulted in 100% survival (10/10). In the Control groups, that is, mice infected with virus but not treated with a drug, no mice survived until day 10 post-infection (0/10, 0/10).
In a previous paper it was reported that two compounds that interfere with estrogen receptors also protected mice from infection with Ebola Virus. Clomiphene (brand names Clomid and Serophene) is used to treat female infertility due to anovulation. Toremifene (brand name Fareston) is approved for the treatment of advanced metastatic breast cancer. Treatment of mice with Clomiphene resulted in 90% (9/10) survival of the infected mice, while Toremifene resulted in 50% survival (5/10). Again, in the Control groups no mice survived until day 10 (0/10, 0/7).
Finally, another in vitro (tissue culture) test was performed on artificially produced virus-like particles (VLPs) to study the mechanism by which the drugs inhibited the virus. From these experiments it was determined that both compounds inhibited the transport of virus components into the cells’ internal machinery, despite the fact the neither compound inhibited the ability of the intact virus particles to get into the cells. Although the exact mechanisms by which these drugs work in blocking Ebola Virus infection of cells, it seems likely that they are NOT working by the same molecular mechanisms that they use for their “real” jobs.
Thus, it is well worth the effort to continue to study known drugs for unexpected activity in situations other than those for which they are currently in use. Repurposing drugs will also save us lots of time and money with regard to drug development. Who can forget that the little blue pill, Viagra (Sildenafil) was originally developed to treat angina. To my knowledge it hasn’t been tested against Ebola yet, but if Vascor works, why not?!
Johansen LM, DeWald LE, Shoemaker CJ, Hoffstrom BG, Lear-Rooney CM, Stossel A, Nelson E, Delos SE, Simmons JA, Grenier JM, Pierce LT, Pajouhesh H, Lehár J, Hensley LE, Glass PJ, White JM, Olinger GG. 2015. A screen of approved drugs and molecular probes identifies therapeutics with anti-Ebola virus activity. Sci Transl Med. 7(290): 290ra89. doi: 10.1126/scitranslmed.aaa5597.
Johansen LM1, 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. 2013. FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection. Sci Transl Med. 5(190):190ra79. doi: 10.1126/scitranslmed.3005471.
Seppa, N. 2015. An antidepressant may protect against Ebola: Zoloft and another drug keep most mice alive after infection with the virus. Science News, Magazine of the Society for Science and the Public. JUNE 3, 2015. https://www.sciencenews.org/article/antidepressant-may-protect-against-ebola
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