title: Repurposing FDA-approved drugs as therapeutics to treat Rift Valley fever virus infection.
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.
authors.affiliation: National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University Manassas, VA, USA.
authors.forename: Ashwini
authors.initials: A
authors.lastname: Benedict
authors.affiliation: National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University Manassas, VA, USA.
authors.forename: Neha
authors.initials: N
authors.lastname: Bansal
authors.affiliation: National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University Manassas, VA, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Senina
authors.affiliation: National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University Manassas, VA, USA.
authors.forename: Idris
authors.initials: I
authors.lastname: Hooper
authors.affiliation: National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University Manassas, VA, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Lundberg
authors.affiliation: National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University Manassas, VA, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: de la Fuente
authors.affiliation: National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University Manassas, VA, USA.
authors.forename: Aarthi
authors.initials: A
authors.lastname: Narayanan
authors.affiliation: Chemical, Biological, Radiological Defense Division, Naval Surface Warfare Center Dahlgren, VA, USA.
authors.forename: Bradford
authors.initials: B
authors.lastname: Gutting
authors.affiliation: National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University Manassas, VA, USA.
authors.forename: Kylene
authors.initials: K
authors.lastname: Kehn-Hall
keywords: FDA; Raf; replication; rift valley fever virus; sorafenib; viral egress