2. Academic Validation
  3. BCX4430 - A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease

BCX4430 - A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease

  • J Infect Public Health. 2016 May-Jun;9(3):220-6. doi: 10.1016/j.jiph.2016.04.002.
Raymond Taylor 1,  Pravin Kotian 2,  Travis Warren 3,  Rekha Panchal 3,  Sina Bavari 3,  Justin Julander 4,  Sylvia Dobo 2,  Angela Rose 2,  Yahya El-Kattan 2,  Brian Taubenheim 5,  Yarlagadda Babu 2,  William P Sheridan 6
Affiliations

Affiliations

  • 1 BioCryst Pharmaceuticals Inc., Durham, NC, USA. Electronic address: [email protected].
  • 2 BioCryst Pharmaceuticals Inc., Durham, NC, USA.
  • 3 Division of Molecular and Translational Sciences, Therapeutic Discovery Center, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MA, USA.
  • 4 Institute for Antiviral Research, Utah State University, Logan, UT, USA.
  • 5 Wilco Consulting, LLC, Durham, NC, USA.
  • 6 BioCryst Pharmaceuticals Inc., Durham, NC, USA. Electronic address: [email protected].
PMID: 27095300 DOI: 10.1016/j.jiph.2016.04.002
Abstract

The adenosine nucleoside analog BCX4430 is a direct-acting Antiviral drug under investigation for the treatment of serious and life-threatening infections from highly pathogenic viruses, such as the Ebola virus. Cellular kinases phosphorylate BCX4430 to a triphosphate that mimics ATP; viral RNA polymerases incorporate the drug's monophosphate nucleotide into the growing RNA chain, causing premature chain termination. BCX4430 is active in vitro against many RNA viral pathogens, including the filoviruses and emerging infectious agents such as MERS-CoV and SARS-CoV. In vivo, BCX4430 is active after intramuscular, intraperitoneal, and oral administration in a variety of experimental infections. In nonclinical studies involving lethal infections with Ebola virus, Marburg virus, Rift Valley fever virus, and Yellow Fever virus, BCX4430 has demonstrated pronounced efficacy. In experiments conducted in several models, both a reduction in the viral load and an improvement in survival were found to be related to the dose of BCX4430. A Phase 1 clinical trial of intramuscular administration of BCX4430 in healthy subjects is currently ongoing.

Keywords

BCX4430; Ebola virus disease; MERS-CoV; Marburg virus disease; Nucleoside analog; Yellow Fever.

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