Saracatinib Inhibits Middle East Respiratory Syndrome-Coronavirus Replication In Vitro
Identifieur interne : 000816 ( Main/Exploration ); précédent : 000815; suivant : 000817Saracatinib Inhibits Middle East Respiratory Syndrome-Coronavirus Replication In Vitro
Auteurs : Jin Soo Shin [Corée du Sud] ; Eunhye Jung ; Meehyein Kim [Corée du Sud] ; Ralph S. Baric ; Yun Young Go [Corée du Sud]Source :
- Viruses [ 1999-4915 ] ; 2018.
Descripteurs français
- KwdFr :
- Antienzymes (pharmacologie), Antiviraux (pharmacologie), Benzodioxoles (pharmacologie), Bibliothèques de petites molécules, Coronavirus du syndrome respiratoire du Moyen-Orient (), Découverte de médicament, Désoxycytidine (analogues et dérivés), Désoxycytidine (pharmacologie), Humains, Infection croisée, Lignée cellulaire, Quinazolines (pharmacologie), Réplication de l'ADN, Réplication virale (), src-Family kinases (antagonistes et inhibiteurs).
- MESH :
- analogues et dérivés : Désoxycytidine.
- antagonistes et inhibiteurs : src-Family kinases.
- pharmacologie : Antienzymes, Antiviraux, Benzodioxoles, Désoxycytidine, Quinazolines.
- Bibliothèques de petites molécules, Coronavirus du syndrome respiratoire du Moyen-Orient, Découverte de médicament, Humains, Infection croisée, Lignée cellulaire, Réplication de l'ADN, Réplication virale.
English descriptors
- KwdEn :
- Antiviral Agents (pharmacology), Benzodioxoles (pharmacology), Cell Line, Cross Infection, DNA Replication, Deoxycytidine (analogs & derivatives), Deoxycytidine (pharmacology), Drug Discovery, Enzyme Inhibitors (pharmacology), Humans, Middle East Respiratory Syndrome Coronavirus (drug effects), Quinazolines (pharmacology), Small Molecule Libraries, Virus Replication (drug effects), src-Family Kinases (antagonists & inhibitors).
- MESH :
- chemical , analogs & derivatives : Deoxycytidine.
- chemical , antagonists & inhibitors : src-Family Kinases.
- chemical , pharmacology : Antiviral Agents, Benzodioxoles, Deoxycytidine, Enzyme Inhibitors, Quinazolines.
- drug effects : Middle East Respiratory Syndrome Coronavirus, Virus Replication.
- Cell Line, Cross Infection, DNA Replication, Drug Discovery, Humans, Small Molecule Libraries.
Abstract
The Middle East respiratory syndrome-coronavirus (MERS-CoV), first identified in Saudi Arabia, is an emerging zoonotic pathogen that causes severe acute respiratory illness in humans with a high fatality rate. Since its emergence, MERS-CoV continues to spread to countries outside of the Arabian Peninsula and gives rise to sporadic human infections following the entry of infected individuals to other countries, which can precipitate outbreaks similar to the one that occurred in South Korea in 2015. Current therapeutics against MERS-CoV infection have primarily been adapted from previous drugs used for the treatment of severe acute respiratory syndrome. In search of new potential drug candidates, we screened a library composed of 2334 clinically approved drugs and pharmacologically active compounds. The drug saracatinib, a potent inhibitor of Src-family of tyrosine kinases (SFK), was identified as an inhibitor of MERS-CoV replication in vitro. Our results suggest that saracatinib potently inhibits MERS-CoV at the early stages of the viral life cycle in Huh-7 cells, possibly through the suppression of SFK signaling pathways. Furthermore, saracatinib exhibited a synergistic effect with gemcitabine, an anticancer drug with antiviral activity against several RNA viruses. These data indicate that saracatinib alone or in combination with gemcitabine can provide a new therapeutic option for the treatment of MERS-CoV infection.
Url:
DOI: 10.3390/v10060283
PubMed: 29795047
PubMed Central: 6024778
Affiliations:
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Le document en format XML
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id="af1-viruses-10-00283">Virus Research Group, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea;<email>jsshin@krict.re.kr</email> (J.S.S.);<email>e-hyeya@hanmail.net</email> (E.J.);<email>mkim@krict.re.kr</email> (M.K.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-viruses-10-00283">Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141</wicri:regionArea><wicri:noRegion>Daejeon 34141</wicri:noRegion></affiliation></author><author><name sortKey="Jung, Eunhye" sort="Jung, Eunhye" uniqKey="Jung E" first="Eunhye" last="Jung">Eunhye Jung</name><affiliation><nlm:aff id="af1-viruses-10-00283">Virus Research Group, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea;<email>jsshin@krict.re.kr</email> (J.S.S.);<email>e-hyeya@hanmail.net</email> (E.J.);<email>mkim@krict.re.kr</email> (M.K.)</nlm:aff></affiliation></author><author><name sortKey="Kim, Meehyein" sort="Kim, Meehyein" uniqKey="Kim M" first="Meehyein" last="Kim">Meehyein Kim</name><affiliation><nlm:aff id="af1-viruses-10-00283">Virus Research Group, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea;<email>jsshin@krict.re.kr</email> (J.S.S.);<email>e-hyeya@hanmail.net</email> (E.J.);<email>mkim@krict.re.kr</email> (M.K.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-viruses-10-00283">Department of Medicinal Chemistry and Pharmacology, University of Science and Technology, Daejeon 34114, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Medicinal Chemistry and Pharmacology, University of Science and Technology, Daejeon 34114</wicri:regionArea><wicri:noRegion>Daejeon 34114</wicri:noRegion></affiliation></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><affiliation><nlm:aff id="af4-viruses-10-00283">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;<email>rbaric@email.unc.edu</email></nlm:aff></affiliation></author><author><name sortKey="Go, Yun Young" sort="Go, Yun Young" uniqKey="Go Y" first="Yun Young" last="Go">Yun Young Go</name><affiliation><nlm:aff id="af1-viruses-10-00283">Virus Research Group, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea;<email>jsshin@krict.re.kr</email> (J.S.S.);<email>e-hyeya@hanmail.net</email> (E.J.);<email>mkim@krict.re.kr</email> (M.K.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-viruses-10-00283">Department of Medicinal Chemistry and Pharmacology, University of Science and Technology, Daejeon 34114, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Medicinal Chemistry and Pharmacology, University of Science and Technology, Daejeon 34114</wicri:regionArea><wicri:noRegion>Daejeon 34114</wicri:noRegion></affiliation></author></analytic><series><title level="j">Viruses</title><idno type="eISSN">1999-4915</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral Agents (pharmacology)</term><term>Benzodioxoles (pharmacology)</term><term>Cell Line</term><term>Cross Infection</term><term>DNA Replication</term><term>Deoxycytidine (analogs & derivatives)</term><term>Deoxycytidine (pharmacology)</term><term>Drug Discovery</term><term>Enzyme Inhibitors (pharmacology)</term><term>Humans</term><term>Middle East Respiratory Syndrome Coronavirus (drug effects)</term><term>Quinazolines (pharmacology)</term><term>Small Molecule Libraries</term><term>Virus Replication (drug effects)</term><term>src-Family Kinases (antagonists & inhibitors)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Antienzymes (pharmacologie)</term><term>Antiviraux (pharmacologie)</term><term>Benzodioxoles (pharmacologie)</term><term>Bibliothèques de petites molécules</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient ()</term><term>Découverte de médicament</term><term>Désoxycytidine (analogues et dérivés)</term><term>Désoxycytidine (pharmacologie)</term><term>Humains</term><term>Infection croisée</term><term>Lignée cellulaire</term><term>Quinazolines (pharmacologie)</term><term>Réplication de l'ADN</term><term>Réplication virale ()</term><term>src-Family kinases (antagonistes et inhibiteurs)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Deoxycytidine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>src-Family Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term><term>Benzodioxoles</term><term>Deoxycytidine</term><term>Enzyme Inhibitors</term><term>Quinazolines</term></keywords><keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Désoxycytidine</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>src-Family kinases</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antienzymes</term><term>Antiviraux</term><term>Benzodioxoles</term><term>Désoxycytidine</term><term>Quinazolines</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line</term><term>Cross Infection</term><term>DNA Replication</term><term>Drug Discovery</term><term>Humans</term><term>Small Molecule Libraries</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Bibliothèques de petites molécules</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Découverte de médicament</term><term>Humains</term><term>Infection croisée</term><term>Lignée cellulaire</term><term>Réplication de l'ADN</term><term>Réplication virale</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The Middle East respiratory syndrome-coronavirus (MERS-CoV), first identified in Saudi Arabia, is an emerging zoonotic pathogen that causes severe acute respiratory illness in humans with a high fatality rate. Since its emergence, MERS-CoV continues to spread to countries outside of the Arabian Peninsula and gives rise to sporadic human infections following the entry of infected individuals to other countries, which can precipitate outbreaks similar to the one that occurred in South Korea in 2015. Current therapeutics against MERS-CoV infection have primarily been adapted from previous drugs used for the treatment of severe acute respiratory syndrome. In search of new potential drug candidates, we screened a library composed of 2334 clinically approved drugs and pharmacologically active compounds. The drug saracatinib, a potent inhibitor of Src-family of tyrosine kinases (SFK), was identified as an inhibitor of MERS-CoV replication in vitro. Our results suggest that saracatinib potently inhibits MERS-CoV at the early stages of the viral life cycle in Huh-7 cells, possibly through the suppression of SFK signaling pathways. Furthermore, saracatinib exhibited a synergistic effect with gemcitabine, an anticancer drug with antiviral activity against several RNA viruses. These data indicate that saracatinib alone or in combination with gemcitabine can provide a new therapeutic option for the treatment of MERS-CoV infection.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="De Wit, E" uniqKey="De Wit E">E. De Wit</name></author><author><name sortKey="Van Doremalen, N" uniqKey="Van Doremalen N">N. van Doremalen</name></author><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D. Falzarano</name></author><author><name sortKey="Munster, V J" uniqKey="Munster V">V.J. Munster</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zaki, A M" uniqKey="Zaki A">A.M. 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Yoon</name></author><author><name sortKey="Seong, J" uniqKey="Seong J">J. Seong</name></author><author><name sortKey="Ko, H J" uniqKey="Ko H">H.J. Ko</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Corée du Sud</li></country></list><tree><noCountry><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><name sortKey="Jung, Eunhye" sort="Jung, Eunhye" uniqKey="Jung E" first="Eunhye" last="Jung">Eunhye Jung</name></noCountry><country name="Corée du Sud"><noRegion><name sortKey="Shin, Jin Soo" sort="Shin, Jin Soo" uniqKey="Shin J" first="Jin Soo" last="Shin">Jin Soo Shin</name></noRegion><name sortKey="Go, Yun Young" sort="Go, Yun Young" uniqKey="Go Y" first="Yun Young" last="Go">Yun Young Go</name><name sortKey="Kim, Meehyein" sort="Kim, Meehyein" uniqKey="Kim M" first="Meehyein" last="Kim">Meehyein Kim</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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