BCX4430 - A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease.
Identifieur interne : 006771 ( Main/Exploration ); précédent : 006770; suivant : 006772BCX4430 - A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease.
Auteurs : Raymond Taylor [États-Unis] ; Pravin Kotian [États-Unis] ; Travis Warren [États-Unis] ; Rekha Panchal [États-Unis] ; Sina Bavari [États-Unis] ; Justin Julander [États-Unis] ; Sylvia Dobo [États-Unis] ; Angela Rose [États-Unis] ; Yahya El-Kattan [États-Unis] ; Brian Taubenheim [États-Unis] ; Yarlagadda Babu [États-Unis] ; William P. Sheridan [États-Unis]Source :
- Journal of infection and public health [ 1876-035X ]
Descripteurs français
- KwdFr :
- Administration par voie orale, Animaux, Antiviraux (pharmacologie), Antiviraux (usage thérapeutique), Découverte de médicament (tendances), Essais cliniques de phase I comme sujet, Humains, Infections à virus à ARN (traitement médicamenteux), Infections à virus à ARN (virologie), Injections musculaires, Injections péritoneales, Modèles animaux de maladie humaine, Nucléoside purique (pharmacologie), Nucléoside purique (usage thérapeutique), Réplication virale (), Résultat thérapeutique, Virus à ARN (), Virus à ARN (physiologie).
- MESH :
- pharmacologie : Antiviraux, Nucléoside purique.
- physiologie : Virus à ARN.
- tendances : Découverte de médicament.
- traitement médicamenteux : Infections à virus à ARN.
- usage thérapeutique : Antiviraux, Nucléoside purique.
- virologie : Infections à virus à ARN.
- Administration par voie orale, Animaux, Essais cliniques de phase I comme sujet, Humains, Injections musculaires, Injections péritoneales, Modèles animaux de maladie humaine, Réplication virale, Résultat thérapeutique, Virus à ARN.
English descriptors
- KwdEn :
- Administration, Oral, Animals, Antiviral Agents (pharmacology), Antiviral Agents (therapeutic use), Clinical Trials, Phase I as Topic, Disease Models, Animal, Drug Discovery (trends), Humans, Injections, Intramuscular, Injections, Intraperitoneal, Purine Nucleosides (pharmacology), Purine Nucleosides (therapeutic use), RNA Virus Infections (drug therapy), RNA Virus Infections (virology), RNA Viruses (drug effects), RNA Viruses (physiology), Treatment Outcome, Virus Replication (drug effects).
- MESH :
- chemical , pharmacology : Antiviral Agents, Purine Nucleosides.
- chemical , therapeutic use : Antiviral Agents, Purine Nucleosides.
- drug effects : RNA Viruses, Virus Replication.
- drug therapy : RNA Virus Infections.
- physiology : RNA Viruses.
- trends : Drug Discovery.
- virology : RNA Virus Infections.
- Administration, Oral, Animals, Clinical Trials, Phase I as Topic, Disease Models, Animal, Humans, Injections, Intramuscular, Injections, Intraperitoneal, Treatment Outcome.
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.
DOI: 10.1016/j.jiph.2016.04.002
PubMed: 27095300
Affiliations:
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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. </div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Caroline du Nord</li><li>Massachusetts</li><li>Utah</li></region></list><tree><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Taylor, Raymond" sort="Taylor, Raymond" uniqKey="Taylor R" first="Raymond" last="Taylor">Raymond Taylor</name></region><name sortKey="Babu, Yarlagadda" sort="Babu, Yarlagadda" uniqKey="Babu Y" first="Yarlagadda" last="Babu">Yarlagadda Babu</name><name sortKey="Bavari, Sina" sort="Bavari, Sina" uniqKey="Bavari S" first="Sina" last="Bavari">Sina Bavari</name><name sortKey="Dobo, Sylvia" sort="Dobo, Sylvia" uniqKey="Dobo S" first="Sylvia" last="Dobo">Sylvia Dobo</name><name sortKey="El Kattan, Yahya" sort="El Kattan, Yahya" uniqKey="El Kattan Y" first="Yahya" last="El-Kattan">Yahya El-Kattan</name><name sortKey="Julander, Justin" sort="Julander, Justin" uniqKey="Julander J" first="Justin" last="Julander">Justin Julander</name><name sortKey="Kotian, Pravin" sort="Kotian, Pravin" uniqKey="Kotian P" first="Pravin" last="Kotian">Pravin Kotian</name><name sortKey="Panchal, Rekha" sort="Panchal, Rekha" uniqKey="Panchal R" first="Rekha" last="Panchal">Rekha Panchal</name><name sortKey="Rose, Angela" sort="Rose, Angela" uniqKey="Rose A" first="Angela" last="Rose">Angela Rose</name><name sortKey="Sheridan, William P" sort="Sheridan, William P" uniqKey="Sheridan W" first="William P" last="Sheridan">William P. Sheridan</name><name sortKey="Taubenheim, Brian" sort="Taubenheim, Brian" uniqKey="Taubenheim B" first="Brian" last="Taubenheim">Brian Taubenheim</name><name sortKey="Warren, Travis" sort="Warren, Travis" uniqKey="Warren T" first="Travis" last="Warren">Travis Warren</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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