BCX4430 – A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease
Summary: 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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-05-01
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| Series: | Journal of Infection and Public Health |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1876034116300193 |
| _version_ | 1818293399858446336 |
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| author | Raymond Taylor Pravin Kotian Travis Warren Rekha Panchal Sina Bavari Justin Julander Sylvia Dobo Angela Rose Yahya El-Kattan Brian Taubenheim Yarlagadda Babu William P. Sheridan |
| author_facet | Raymond Taylor Pravin Kotian Travis Warren Rekha Panchal Sina Bavari Justin Julander Sylvia Dobo Angela Rose Yahya El-Kattan Brian Taubenheim Yarlagadda Babu William P. Sheridan |
| author_sort | Raymond Taylor |
| collection | DOAJ |
| description | Summary: 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, Nucleoside analog, Ebola virus disease, Marburg virus disease, MERS-CoV, Yellow Fever |
| first_indexed | 2024-12-13T03:15:15Z |
| format | Article |
| id | doaj.art-ba1085a16a5c4127997d05edf8a63213 |
| institution | Directory Open Access Journal |
| issn | 1876-0341 |
| language | English |
| last_indexed | 2024-12-13T03:15:15Z |
| publishDate | 2016-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Infection and Public Health |
| spelling | doaj.art-ba1085a16a5c4127997d05edf8a632132022-12-22T00:01:29ZengElsevierJournal of Infection and Public Health1876-03412016-05-0193220226BCX4430 – A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus diseaseRaymond Taylor0Pravin Kotian1Travis Warren2Rekha Panchal3Sina Bavari4Justin Julander5Sylvia Dobo6Angela Rose7Yahya El-Kattan8Brian Taubenheim9Yarlagadda Babu10William P. Sheridan11BioCryst Pharmaceuticals Inc., Durham, NC, USABioCryst Pharmaceuticals Inc., Durham, NC, USADivision of Molecular and Translational Sciences, Therapeutic Discovery Center, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MA, USADivision of Molecular and Translational Sciences, Therapeutic Discovery Center, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MA, USADivision of Molecular and Translational Sciences, Therapeutic Discovery Center, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MA, USAInstitute for Antiviral Research, Utah State University, Logan, UT, USABioCryst Pharmaceuticals Inc., Durham, NC, USABioCryst Pharmaceuticals Inc., Durham, NC, USABioCryst Pharmaceuticals Inc., Durham, NC, USAWilco Consulting, LLC, Durham, NC, USABioCryst Pharmaceuticals Inc., Durham, NC, USABioCryst Pharmaceuticals Inc., Durham, NC, USA; Corresponding author at: BioCryst Pharmaceuticals Inc., 4505 Emperor Boulevard, Suite 200, Durham, NC 27703, USA. Tel.: +1 919 859 7906.Summary: 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, Nucleoside analog, Ebola virus disease, Marburg virus disease, MERS-CoV, Yellow Feverhttp://www.sciencedirect.com/science/article/pii/S1876034116300193 |
| spellingShingle | Raymond Taylor Pravin Kotian Travis Warren Rekha Panchal Sina Bavari Justin Julander Sylvia Dobo Angela Rose Yahya El-Kattan Brian Taubenheim Yarlagadda Babu William P. Sheridan BCX4430 – A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease Journal of Infection and Public Health |
| title | BCX4430 – A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease |
| title_full | BCX4430 – A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease |
| title_fullStr | BCX4430 – A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease |
| title_full_unstemmed | BCX4430 – A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease |
| title_short | BCX4430 – A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease |
| title_sort | bcx4430 a broad spectrum antiviral adenosine nucleoside analog under development for the treatment of ebola virus disease |
| url | http://www.sciencedirect.com/science/article/pii/S1876034116300193 |
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