BCX4430 - A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease.
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.
BioCryst Pharmaceuticals Inc., Durham, NC, USA. Electronic address: rtaylor@BIOCRYST.com.
Raymond
R
Taylor
BioCryst Pharmaceuticals Inc., Durham, NC, USA.
Pravin
P
Kotian
Division of Molecular and Translational Sciences, Therapeutic Discovery Center, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MA, USA.
Travis
T
Warren
Division of Molecular and Translational Sciences, Therapeutic Discovery Center, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MA, USA.
Rekha
R
Panchal
Division of Molecular and Translational Sciences, Therapeutic Discovery Center, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MA, USA.
Sina
S
Bavari
Institute for Antiviral Research, Utah State University, Logan, UT, USA.
Justin
J
Julander
BioCryst Pharmaceuticals Inc., Durham, NC, USA.
Sylvia
S
Dobo
BioCryst Pharmaceuticals Inc., Durham, NC, USA.
Angela
A
Rose
BioCryst Pharmaceuticals Inc., Durham, NC, USA.
Yahya
Y
El-Kattan
Wilco Consulting, LLC, Durham, NC, USA.
Brian
B
Taubenheim
BioCryst Pharmaceuticals Inc., Durham, NC, USA.
Yarlagadda
Y
Babu
BioCryst Pharmaceuticals Inc., Durham, NC, USA. Electronic address: bsheridan@biocryst.com.
William P
WP
Sheridan
D000225:Adenine / Q000031:analogs & derivatives; D000241:Adenosine / Q000031:analogs & derivatives; D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000639:trends; D006801:Humans; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D011684:Purine Nucleosides / Q000494:pharmacology* / Q000627:therapeutic use*; D011759:Pyrrolidines; D012327:RNA Virus Infections / Q000188:drug therapy* / Q000821:virology; D012328:RNA Viruses / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D011684:Purine Nucleosides; D011759:Pyrrolidines; D000225:Adenine; D000241:Adenosine; C517546:galidesivir
BCX4430; Ebola virus disease; MERS-CoV; Marburg virus disease; Nucleoside analog; Yellow Fever