Repurposing FDA-approved drugs as therapeutics to treat Rift Valley fever virus infection
Date
2015-07-08
Authors
Benedict, Ashwini
Bansal, Neha
Senina, Svetlana
Hooper, Idris
Lundberg, Lindsay
de la Fuente, Cynthia
Narayanan, Aarthi
Gutting, Bradford
Kehn-Hall, Kylene
Journal Title
Journal ISSN
Volume Title
Publisher
Frontiers
Abstract
There 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.
Description
Keywords
Rift Valley Fever virus, Raf, Sorafenib, Viral egress, Replication, FDA
Citation
Benedict 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