BCX4430 - A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease.
Identifieur interne : 001158 ( PubMed/Corpus ); précédent : 001157; suivant : 001159BCX4430 - A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease.
Auteurs : 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. SheridanSource :
- Journal of infection and public health [ 1876-035X ]
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
Links to Exploration step
pubmed:27095300Le document en format XML
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Electronic address: rtaylor@BIOCRYST.com.</nlm:affiliation></affiliation></author><author><name sortKey="Kotian, Pravin" sort="Kotian, Pravin" uniqKey="Kotian P" first="Pravin" last="Kotian">Pravin Kotian</name><affiliation><nlm:affiliation>BioCryst Pharmaceuticals Inc., Durham, NC, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Warren, Travis" sort="Warren, Travis" uniqKey="Warren T" first="Travis" last="Warren">Travis Warren</name><affiliation><nlm:affiliation>Division of Molecular and Translational Sciences, Therapeutic Discovery Center, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Panchal, Rekha" sort="Panchal, Rekha" uniqKey="Panchal R" first="Rekha" last="Panchal">Rekha Panchal</name><affiliation><nlm:affiliation>Division of Molecular and Translational Sciences, Therapeutic Discovery Center, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Bavari, Sina" sort="Bavari, Sina" uniqKey="Bavari S" first="Sina" last="Bavari">Sina Bavari</name><affiliation><nlm:affiliation>Division of Molecular and Translational Sciences, Therapeutic Discovery Center, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Julander, Justin" sort="Julander, Justin" uniqKey="Julander J" first="Justin" last="Julander">Justin Julander</name><affiliation><nlm:affiliation>Institute for Antiviral Research, Utah State University, Logan, UT, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Dobo, Sylvia" sort="Dobo, Sylvia" uniqKey="Dobo S" first="Sylvia" last="Dobo">Sylvia Dobo</name><affiliation><nlm:affiliation>BioCryst Pharmaceuticals Inc., Durham, NC, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Rose, Angela" sort="Rose, Angela" uniqKey="Rose A" first="Angela" last="Rose">Angela Rose</name><affiliation><nlm:affiliation>BioCryst Pharmaceuticals Inc., Durham, NC, USA.</nlm:affiliation></affiliation></author><author><name sortKey="El Kattan, Yahya" sort="El Kattan, Yahya" uniqKey="El Kattan Y" first="Yahya" last="El-Kattan">Yahya El-Kattan</name><affiliation><nlm:affiliation>BioCryst Pharmaceuticals Inc., Durham, NC, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Taubenheim, Brian" sort="Taubenheim, Brian" uniqKey="Taubenheim B" first="Brian" last="Taubenheim">Brian Taubenheim</name><affiliation><nlm:affiliation>Wilco Consulting, LLC, Durham, NC, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Babu, Yarlagadda" sort="Babu, Yarlagadda" uniqKey="Babu Y" first="Yarlagadda" last="Babu">Yarlagadda Babu</name><affiliation><nlm:affiliation>BioCryst Pharmaceuticals Inc., Durham, NC, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Sheridan, William P" sort="Sheridan, William P" uniqKey="Sheridan W" first="William P" last="Sheridan">William P. Sheridan</name><affiliation><nlm:affiliation>BioCryst Pharmaceuticals Inc., Durham, NC, USA. 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Electronic address: rtaylor@BIOCRYST.com.</nlm:affiliation></affiliation></author><author><name sortKey="Kotian, Pravin" sort="Kotian, Pravin" uniqKey="Kotian P" first="Pravin" last="Kotian">Pravin Kotian</name><affiliation><nlm:affiliation>BioCryst Pharmaceuticals Inc., Durham, NC, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Warren, Travis" sort="Warren, Travis" uniqKey="Warren T" first="Travis" last="Warren">Travis Warren</name><affiliation><nlm:affiliation>Division of Molecular and Translational Sciences, Therapeutic Discovery Center, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Panchal, Rekha" sort="Panchal, Rekha" uniqKey="Panchal R" first="Rekha" last="Panchal">Rekha Panchal</name><affiliation><nlm:affiliation>Division of Molecular and Translational Sciences, Therapeutic Discovery Center, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Bavari, Sina" sort="Bavari, Sina" uniqKey="Bavari S" first="Sina" last="Bavari">Sina Bavari</name><affiliation><nlm:affiliation>Division of Molecular and Translational Sciences, Therapeutic Discovery Center, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Julander, Justin" sort="Julander, Justin" uniqKey="Julander J" first="Justin" last="Julander">Justin Julander</name><affiliation><nlm:affiliation>Institute for Antiviral Research, Utah State University, Logan, UT, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Dobo, Sylvia" sort="Dobo, Sylvia" uniqKey="Dobo S" first="Sylvia" last="Dobo">Sylvia Dobo</name><affiliation><nlm:affiliation>BioCryst Pharmaceuticals Inc., Durham, NC, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Rose, Angela" sort="Rose, Angela" uniqKey="Rose A" first="Angela" last="Rose">Angela Rose</name><affiliation><nlm:affiliation>BioCryst Pharmaceuticals Inc., Durham, NC, USA.</nlm:affiliation></affiliation></author><author><name sortKey="El Kattan, Yahya" sort="El Kattan, Yahya" uniqKey="El Kattan Y" first="Yahya" last="El-Kattan">Yahya El-Kattan</name><affiliation><nlm:affiliation>BioCryst Pharmaceuticals Inc., Durham, NC, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Taubenheim, Brian" sort="Taubenheim, Brian" uniqKey="Taubenheim B" first="Brian" last="Taubenheim">Brian Taubenheim</name><affiliation><nlm:affiliation>Wilco Consulting, LLC, Durham, NC, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Babu, Yarlagadda" sort="Babu, Yarlagadda" uniqKey="Babu Y" first="Yarlagadda" last="Babu">Yarlagadda Babu</name><affiliation><nlm:affiliation>BioCryst Pharmaceuticals Inc., Durham, NC, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Sheridan, William P" sort="Sheridan, William P" uniqKey="Sheridan W" first="William P" last="Sheridan">William P. Sheridan</name><affiliation><nlm:affiliation>BioCryst Pharmaceuticals Inc., Durham, NC, USA. Electronic address: bsheridan@biocryst.com.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Journal of infection and public health</title><idno type="eISSN">1876-035X</idno></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Administration, Oral</term><term>Animals</term><term>Antiviral Agents (pharmacology)</term><term>Antiviral Agents (therapeutic use)</term><term>Clinical Trials, Phase I as Topic</term><term>Disease Models, Animal</term><term>Drug Discovery (trends)</term><term>Humans</term><term>Injections, Intramuscular</term><term>Injections, Intraperitoneal</term><term>Purine Nucleosides (pharmacology)</term><term>Purine Nucleosides (therapeutic use)</term><term>RNA Virus Infections (drug therapy)</term><term>RNA Virus Infections (virology)</term><term>RNA Viruses (drug effects)</term><term>RNA Viruses (physiology)</term><term>Treatment Outcome</term><term>Virus Replication (drug effects)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term><term>Purine Nucleosides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiviral Agents</term><term>Purine Nucleosides</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>RNA Viruses</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>RNA Virus Infections</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>RNA Viruses</term></keywords><keywords scheme="MESH" qualifier="trends" xml:lang="en"><term>Drug Discovery</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>RNA Virus Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Administration, Oral</term><term>Animals</term><term>Clinical Trials, Phase I as Topic</term><term>Disease Models, Animal</term><term>Humans</term><term>Injections, Intramuscular</term><term>Injections, Intraperitoneal</term><term>Treatment Outcome</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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. </div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27095300</PMID><DateCompleted><Year>2017</Year><Month>01</Month><Day>30</Day></DateCompleted><DateRevised><Year>2020</Year><Month>03</Month><Day>16</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1876-035X</ISSN><JournalIssue CitedMedium="Internet"><Volume>9</Volume><Issue>3</Issue><PubDate><MedlineDate>2016 May-Jun</MedlineDate></PubDate></JournalIssue><Title>Journal of infection and public health</Title><ISOAbbreviation>J Infect Public Health</ISOAbbreviation></Journal><ArticleTitle>BCX4430 - A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease.</ArticleTitle><Pagination><MedlinePgn>220-6</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.jiph.2016.04.002</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S1876-0341(16)30019-3</ELocationID><Abstract><AbstractText>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. </AbstractText><CopyrightInformation>Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Taylor</LastName><ForeName>Raymond</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>BioCryst Pharmaceuticals Inc., Durham, NC, USA. Electronic address: rtaylor@BIOCRYST.com.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kotian</LastName><ForeName>Pravin</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>BioCryst Pharmaceuticals Inc., Durham, NC, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Warren</LastName><ForeName>Travis</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Division of Molecular and Translational Sciences, Therapeutic Discovery Center, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Panchal</LastName><ForeName>Rekha</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Division of Molecular and Translational Sciences, Therapeutic Discovery Center, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bavari</LastName><ForeName>Sina</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Division of Molecular and Translational Sciences, Therapeutic Discovery Center, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Julander</LastName><ForeName>Justin</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Institute for Antiviral Research, Utah State University, Logan, UT, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dobo</LastName><ForeName>Sylvia</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>BioCryst Pharmaceuticals Inc., Durham, NC, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rose</LastName><ForeName>Angela</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>BioCryst Pharmaceuticals Inc., Durham, NC, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>El-Kattan</LastName><ForeName>Yahya</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>BioCryst Pharmaceuticals Inc., Durham, NC, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Taubenheim</LastName><ForeName>Brian</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Wilco Consulting, LLC, Durham, NC, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Babu</LastName><ForeName>Yarlagadda</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>BioCryst Pharmaceuticals Inc., Durham, NC, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sheridan</LastName><ForeName>William P</ForeName><Initials>WP</Initials><AffiliationInfo><Affiliation>BioCryst Pharmaceuticals Inc., Durham, NC, USA. Electronic address: bsheridan@biocryst.com.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>HHSN272201300017C</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>HHSN272201300017I</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>04</Month><Day>16</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>J Infect Public Health</MedlineTA><NlmUniqueID>101487384</NlmUniqueID><ISSNLinking>1876-0341</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011684">Purine Nucleosides</NameOfSubstance></Chemical><Chemical><RegistryNumber>OLF97F86A7</RegistryNumber><NameOfSubstance UI="C517546">immucillin A</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000284" MajorTopicYN="N">Administration, Oral</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017321" MajorTopicYN="N">Clinical Trials, Phase I as Topic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease 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MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012328" MajorTopicYN="N">RNA Viruses</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016896" MajorTopicYN="N">Treatment Outcome</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014779" MajorTopicYN="N">Virus Replication</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">BCX4430</Keyword><Keyword MajorTopicYN="N">Ebola virus disease</Keyword><Keyword MajorTopicYN="N">MERS-CoV</Keyword><Keyword MajorTopicYN="N">Marburg virus disease</Keyword><Keyword MajorTopicYN="N">Nucleoside analog</Keyword><Keyword MajorTopicYN="N">Yellow Fever</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>03</Month><Day>14</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2016</Year><Month>03</Month><Day>21</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>04</Month><Day>02</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>4</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>4</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>1</Month><Day>31</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">27095300</ArticleId><ArticleId IdType="pii">S1876-0341(16)30019-3</ArticleId><ArticleId IdType="doi">10.1016/j.jiph.2016.04.002</ArticleId><ArticleId IdType="pmc">PMC4937725</ArticleId><ArticleId 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