Protease inhibitors targeting coronavirus and filovirus entry
Identifieur interne : 001612 ( Main/Exploration ); précédent : 001611; suivant : 001613Protease inhibitors targeting coronavirus and filovirus entry
Auteurs : Yanchen Zhou [États-Unis] ; Punitha Vedantham [États-Unis] ; Kai Lu [États-Unis] ; Juliet Agudelo [États-Unis] ; Ricardo Carrion [États-Unis] ; Jerritt W. Nunneley [États-Unis] ; Dale Barnard [États-Unis] ; Stefan Pöhlmann [Allemagne] ; James H. Mckerrow [États-Unis] ; Adam R. Renslo [États-Unis] ; Graham Simmons [États-Unis]Source :
- Antiviral Research [ 0166-3542 ] ; 2015.
Descripteurs français
- KwdFr :
- Animaux, Antiviraux (pharmacologie), Cathepsines (métabolisme), Composés vinyliques (pharmacologie), Coronavirus (), Coronavirus (physiologie), Dipeptides (pharmacologie), Ebolavirus (), Ebolavirus (physiologie), Filoviridae (), Filoviridae (physiologie), Gabexate (analogues et dérivés), Gabexate (pharmacologie), Humains, Infections à coronavirus (traitement médicamenteux), Inhibiteurs de la sérine protéinase (pharmacologie), Inhibiteurs de protéases (pharmacologie), Lignée cellulaire tumorale, Pénétration virale (), Serine endopeptidases (métabolisme), Souris, Souris de lignée BALB C, Virus du SRAS (), Virus du SRAS (physiologie).
- MESH :
- analogues et dérivés : Gabexate.
- métabolisme : Cathepsines, Serine endopeptidases.
- pharmacologie : Antiviraux, Composés vinyliques, Dipeptides, Gabexate, Inhibiteurs de la sérine protéinase, Inhibiteurs de protéases.
- physiologie : Coronavirus, Ebolavirus, Filoviridae, Virus du SRAS.
- traitement médicamenteux : Infections à coronavirus.
- Animaux, Coronavirus, Ebolavirus, Filoviridae, Humains, Lignée cellulaire tumorale, Pénétration virale, Souris, Souris de lignée BALB C, Virus du SRAS.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (pharmacology), Cathepsins (metabolism), Cell Line, Tumor, Coronavirus (drug effects), Coronavirus (physiology), Coronavirus Infections (drug therapy), Dipeptides (pharmacology), Ebolavirus (drug effects), Ebolavirus (physiology), Filoviridae (drug effects), Filoviridae (physiology), Gabexate (analogs & derivatives), Gabexate (pharmacology), Humans, Mice, Mice, Inbred BALB C, Protease Inhibitors (pharmacology), SARS Virus (drug effects), SARS Virus (physiology), Serine Endopeptidases (metabolism), Serine Proteinase Inhibitors (pharmacology), Vinyl Compounds (pharmacology), Virus Internalization (drug effects).
- MESH :
- chemical , analogs & derivatives : Gabexate.
- chemical , metabolism : Cathepsins, Serine Endopeptidases.
- chemical , pharmacology : Antiviral Agents, Dipeptides, Gabexate, Protease Inhibitors, Serine Proteinase Inhibitors, Vinyl Compounds.
- drug effects : Coronavirus, Ebolavirus, Filoviridae, SARS Virus, Virus Internalization.
- drug therapy : Coronavirus Infections.
- physiology : Coronavirus, Ebolavirus, Filoviridae, SARS Virus.
- Animals, Cell Line, Tumor, Humans, Mice, Mice, Inbred BALB C.
Abstract
We identify vinylsulfones as lead candidate inhibitors of Ebola virus and SARS-CoV. K11777 inhibited Ebola virus and SARS-CoV entry in the sub-nanomolar range. Potent inhibition correlated with the presence of a basic piperazine ring at P3. Serine protease inhibitor and K11777 blocked coronavirus entry into caco-2 cells. Camostat protected 6 out of ten mice from lethal infection with SARS-CoV.
Url:
DOI: 10.1016/j.antiviral.2015.01.011
PubMed: 25666761
PubMed Central: 4774534
Affiliations:
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Le document en format XML
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xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94118</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Vedantham, Punitha" sort="Vedantham, Punitha" uniqKey="Vedantham P" first="Punitha" last="Vedantham">Punitha Vedantham</name><affiliation wicri:level="2"><nlm:aff id="af015">Small Molecule Discovery Center and Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Small Molecule Discovery Center and Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Lu, Kai" sort="Lu, Kai" uniqKey="Lu K" first="Kai" last="Lu">Kai Lu</name><affiliation wicri:level="2"><nlm:aff id="af005">Blood Systems Research Institute, San Francisco, CA 94118, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Blood Systems Research Institute, San Francisco, CA 94118</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Agudelo, Juliet" sort="Agudelo, Juliet" uniqKey="Agudelo J" first="Juliet" last="Agudelo">Juliet Agudelo</name><affiliation wicri:level="2"><nlm:aff id="af005">Blood Systems Research Institute, San Francisco, CA 94118, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Blood Systems Research Institute, San Francisco, CA 94118</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Carrion, Ricardo" sort="Carrion, Ricardo" uniqKey="Carrion R" first="Ricardo" last="Carrion">Ricardo Carrion</name><affiliation wicri:level="2"><nlm:aff id="af020">Texas Biomedical Research Institute, San Antonio, TX 78227, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Texas Biomedical Research Institute, San Antonio, TX 78227</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Nunneley, Jerritt W" sort="Nunneley, Jerritt W" uniqKey="Nunneley J" first="Jerritt W." last="Nunneley">Jerritt W. Nunneley</name><affiliation wicri:level="2"><nlm:aff id="af020">Texas Biomedical Research Institute, San Antonio, TX 78227, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Texas Biomedical Research Institute, San Antonio, TX 78227</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Barnard, Dale" sort="Barnard, Dale" uniqKey="Barnard D" first="Dale" last="Barnard">Dale Barnard</name><affiliation wicri:level="2"><nlm:aff id="af025">Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Science, Utah State University, Logan, UT 84322, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Science, Utah State University, Logan, UT 84322</wicri:regionArea><placeName><region type="state">Utah</region></placeName></affiliation></author><author><name sortKey="Pohlmann, Stefan" sort="Pohlmann, Stefan" uniqKey="Pohlmann S" first="Stefan" last="Pöhlmann">Stefan Pöhlmann</name><affiliation wicri:level="3"><nlm:aff id="af030">Infection Biology Unit, German Primate Center, 37077 Göttingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Infection Biology Unit, German Primate Center, 37077 Göttingen</wicri:regionArea><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Göttingen</settlement></placeName></affiliation></author><author><name sortKey="Mckerrow, James H" sort="Mckerrow, James H" uniqKey="Mckerrow J" first="James H." last="Mckerrow">James H. Mckerrow</name><affiliation wicri:level="2"><nlm:aff id="af035">Department of Pathology and Center for Discovery and Innovation in Parasitic Diseases, University of California, San Francisco, San Francisco, CA 94158, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Center for Discovery and Innovation in Parasitic Diseases, University of California, San Francisco, San Francisco, CA 94158</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Renslo, Adam R" sort="Renslo, Adam R" uniqKey="Renslo A" first="Adam R." last="Renslo">Adam R. Renslo</name><affiliation wicri:level="2"><nlm:aff id="af015">Small Molecule Discovery Center and Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Small Molecule Discovery Center and Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Simmons, Graham" sort="Simmons, Graham" uniqKey="Simmons G" first="Graham" last="Simmons">Graham Simmons</name><affiliation wicri:level="2"><nlm:aff id="af005">Blood Systems Research Institute, San Francisco, CA 94118, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Blood Systems Research Institute, San Francisco, CA 94118</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="af010">Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94118, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94118</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author></analytic><series><title level="j">Antiviral Research</title><idno type="ISSN">0166-3542</idno><idno type="eISSN">1872-9096</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antiviral Agents (pharmacology)</term><term>Cathepsins (metabolism)</term><term>Cell Line, Tumor</term><term>Coronavirus (drug effects)</term><term>Coronavirus (physiology)</term><term>Coronavirus Infections (drug therapy)</term><term>Dipeptides (pharmacology)</term><term>Ebolavirus (drug effects)</term><term>Ebolavirus (physiology)</term><term>Filoviridae (drug effects)</term><term>Filoviridae (physiology)</term><term>Gabexate (analogs & derivatives)</term><term>Gabexate (pharmacology)</term><term>Humans</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Protease Inhibitors (pharmacology)</term><term>SARS Virus (drug effects)</term><term>SARS Virus (physiology)</term><term>Serine Endopeptidases (metabolism)</term><term>Serine Proteinase Inhibitors (pharmacology)</term><term>Vinyl Compounds (pharmacology)</term><term>Virus Internalization (drug effects)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antiviraux (pharmacologie)</term><term>Cathepsines (métabolisme)</term><term>Composés vinyliques (pharmacologie)</term><term>Coronavirus ()</term><term>Coronavirus (physiologie)</term><term>Dipeptides (pharmacologie)</term><term>Ebolavirus ()</term><term>Ebolavirus (physiologie)</term><term>Filoviridae ()</term><term>Filoviridae (physiologie)</term><term>Gabexate (analogues et dérivés)</term><term>Gabexate (pharmacologie)</term><term>Humains</term><term>Infections à coronavirus (traitement médicamenteux)</term><term>Inhibiteurs de la sérine protéinase (pharmacologie)</term><term>Inhibiteurs de protéases (pharmacologie)</term><term>Lignée cellulaire tumorale</term><term>Pénétration virale ()</term><term>Serine endopeptidases (métabolisme)</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Virus du SRAS ()</term><term>Virus du SRAS (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Gabexate</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cathepsins</term><term>Serine Endopeptidases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term><term>Dipeptides</term><term>Gabexate</term><term>Protease Inhibitors</term><term>Serine Proteinase Inhibitors</term><term>Vinyl Compounds</term></keywords><keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Gabexate</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Coronavirus</term><term>Ebolavirus</term><term>Filoviridae</term><term>SARS Virus</term><term>Virus Internalization</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cathepsines</term><term>Serine endopeptidases</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term><term>Composés vinyliques</term><term>Dipeptides</term><term>Gabexate</term><term>Inhibiteurs de la sérine protéinase</term><term>Inhibiteurs de protéases</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Coronavirus</term><term>Ebolavirus</term><term>Filoviridae</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Coronavirus</term><term>Ebolavirus</term><term>Filoviridae</term><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Humans</term><term>Mice</term><term>Mice, Inbred BALB C</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Coronavirus</term><term>Ebolavirus</term><term>Filoviridae</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Pénétration virale</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Virus du SRAS</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Highlights</title><p><list list-type="simple" id="l0005"><list-item id="o0005"><label>•</label><p id="p0005">We identify vinylsulfones as lead candidate inhibitors of Ebola virus and SARS-CoV.</p></list-item><list-item id="o0010"><label>•</label><p id="p0010">K11777 inhibited Ebola virus and SARS-CoV entry in the sub-nanomolar range.</p></list-item><list-item id="o0015"><label>•</label><p id="p0015">Potent inhibition correlated with the presence of a basic piperazine ring at P3.</p></list-item><list-item id="o0020"><label>•</label><p id="p0020">Serine protease inhibitor and K11777 blocked coronavirus entry into caco-2 cells.</p></list-item><list-item id="o0025"><label>•</label><p id="p0025">Camostat protected 6 out of ten mice from lethal infection with SARS-CoV.</p></list-item></list></p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name 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Renslo</name><name sortKey="Simmons, Graham" sort="Simmons, Graham" uniqKey="Simmons G" first="Graham" last="Simmons">Graham Simmons</name><name sortKey="Simmons, Graham" sort="Simmons, Graham" uniqKey="Simmons G" first="Graham" last="Simmons">Graham Simmons</name><name sortKey="Vedantham, Punitha" sort="Vedantham, Punitha" uniqKey="Vedantham P" first="Punitha" last="Vedantham">Punitha Vedantham</name><name sortKey="Zhou, Yanchen" sort="Zhou, Yanchen" uniqKey="Zhou Y" first="Yanchen" last="Zhou">Yanchen Zhou</name></country><country name="Allemagne"><region name="Basse-Saxe"><name sortKey="Pohlmann, Stefan" sort="Pohlmann, Stefan" uniqKey="Pohlmann S" first="Stefan" last="Pöhlmann">Stefan Pöhlmann</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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