Repurposing FDA-approved drugs as therapeutics to treat Rift Valley fever virus infection

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dc.contributor.authorBenedict, Ashwini
dc.contributor.authorBansal, Neha
dc.contributor.authorSenina, Svetlana
dc.contributor.authorHooper, Idris
dc.contributor.authorLundberg, Lindsay
dc.contributor.authorde la Fuente, Cynthia
dc.contributor.authorNarayanan, Aarthi
dc.contributor.authorGutting, Bradford
dc.contributor.authorKehn-Hall, Kylene
dc.date.accessioned2016-08-09T00:17:04Z
dc.date.available2016-08-09T00:17:04Z
dc.date.issued2015-07-08
dc.description.abstractThere are currently no FDA-approved therapeutics available to treat Rift Valley fever virus (RVFV) infection. In an effort to repurpose drugs for RVFV treatment, a library of FDA-approved drugs was screened to determine their ability to inhibit RVFV. Several drugs from varying compound classes, including inhibitors of growth factor receptors, microtubule assembly/disassembly, and DNA synthesis, were found to reduce RVFV replication. The hepatocellular and renal cell carcinoma drug, sorafenib, was the most effective inhibitor, being non-toxic and demonstrating inhibition of RVFV in a cell-type and virus strain independent manner. Mechanism of action studies indicated that sorafenib targets at least two stages in the virus infectious cycle, RNA synthesis and viral egress. Computational modeling studies also support this conclusion. siRNA knockdown of Raf proteins indicated that non-classical targets of sorafenib are likely important for the replication of RVFV.
dc.description.sponsorshipPublication of this article was funded in part by the George Mason University Libraries Open Access Publishing Fund.
dc.identifier.citationBenedict A, Bansal N, Senina S, Hooper I, Lundberg L, de la Fuente C, Narayanan A, Gutting B and Kehn-Hall K (2015) Repurposing FDA-approved drugs as therapeutics to treat Rift Valley fever virus infection. Front. Microbiol. 6:676. doi: 10.3389/fmicb.2015.00676
dc.identifier.doihttp://dx.doi.org/10.3389/fmicb.2015.00676
dc.identifier.urihttps://hdl.handle.net/1920/10335
dc.language.isoen_US
dc.publisherFrontiers
dc.subjectRift Valley Fever virus
dc.subjectRaf
dc.subjectSorafenib
dc.subjectViral egress
dc.subjectReplication
dc.subjectFDA
dc.titleRepurposing FDA-approved drugs as therapeutics to treat Rift Valley fever virus infection
dc.typeArticle

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