HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Inhibition of Rift Valley fever virus replication and perturbation of nucleocapsid-RNA interactions by suramin.

Abstract
Rift Valley fever virus (RVFV) is an emerging infectious pathogen that causes severe disease in humans and livestock and has the potential for global spread. There are currently no proven safe and effective treatment options for RVFV infection. Inhibition of RNA binding to RVFV nucleocapsid protein (N) represents an attractive antiviral therapeutic strategy because several essential steps in the RVFV replication cycle involve N binding to viral RNA. In this study, we demonstrate the therapeutic potential of the drug suramin by showing that it functions well as an inhibitor of RVFV replication at multiple stages in human cell culture. Suramin has been used previously to treat trypanosomiasis in Africa. We characterize the dynamic and cooperative nature of N-RNA binding interactions and the dissociation of high-molecular-mass ribonucleoprotein complexes using suramin, which we previously identified as an N-RNA binding inhibitor in a high-throughput screen. Finally, we elucidate the molecular mechanism used by suramin in vitro to disrupt both specific and nonspecific binding events important for ribonucleoprotein formation.
AuthorsMary Ellenbecker, Jean-Marc Lanchy, J Stephen Lodmell
JournalAntimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 58 Issue 12 Pg. 7405-15 (Dec 2014) ISSN: 1098-6596 [Electronic] United States
PMID25267680 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2014, American Society for Microbiology. All Rights Reserved.
Chemical References
  • Antiviral Agents
  • Nucleocapsid Proteins
  • RNA, Viral
  • Trypanocidal Agents
  • Suramin
Topics
  • Antiviral Agents (pharmacology)
  • Base Sequence
  • Dose-Response Relationship, Drug
  • Drug Repositioning
  • HEK293 Cells
  • Humans
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Nucleocapsid Proteins (antagonists & inhibitors, chemistry, genetics, metabolism)
  • Protein Binding (drug effects)
  • RNA, Viral (antagonists & inhibitors, chemistry, genetics, metabolism)
  • Rift Valley fever virus (drug effects, metabolism, physiology)
  • Suramin (pharmacology)
  • Trypanocidal Agents (pharmacology)
  • Virus Replication (drug effects)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: