HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection.

Abstract
Recent outbreaks of the Ebola virus (EBOV) have focused attention on the dire need for antivirals to treat these patients. We identified pyronaridine tetraphosphate as a potential candidate as it is an approved drug in the European Union which is currently used in combination with artesunate as a treatment for malaria (EC50 between 420 nM-1.14 μM against EBOV in HeLa cells). Range-finding studies in mice directed us to a single 75 mg/kg i.p. dose 1 hr after infection which resulted in 100% survival and statistically significantly reduced viremia at study day 3 from a lethal challenge with mouse-adapted EBOV (maEBOV). Further, an EBOV window study suggested we could dose pyronaridine 2 or 24 hrs post-exposure to result in similar efficacy. Analysis of cytokine and chemokine panels suggests that pyronaridine may act as an immunomodulator during an EBOV infection. Our studies with pyronaridine clearly demonstrate potential utility for its repurposing as an antiviral against EBOV and merits further study in larger animal models with the added benefit of already being used as a treatment against malaria.
AuthorsThomas R Lane, Christopher Massey, Jason E Comer, Manu Anantpadma, Joel S Freundlich, Robert A Davey, Peter B Madrid, Sean Ekins
JournalPLoS neglected tropical diseases (PLoS Negl Trop Dis) Vol. 13 Issue 11 Pg. e0007890 (11 2019) ISSN: 1935-2735 [Electronic] United States
PMID31751347 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antimalarials
  • Antiviral Agents
  • Cytokines
  • Naphthyridines
  • pyronaridine
Topics
  • Animals
  • Antimalarials (administration & dosage, adverse effects, pharmacokinetics)
  • Antiviral Agents (administration & dosage, adverse effects, pharmacokinetics)
  • Cytokines (immunology)
  • Drug Repositioning
  • Ebolavirus (drug effects, genetics, physiology)
  • Female
  • Hemorrhagic Fever, Ebola (immunology, prevention & control, virology)
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Naphthyridines (administration & dosage, adverse effects, pharmacokinetics)

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: