Thiopurine analogues inhibit papain-like protease of severe acute respiratory syndrome coronavirus.
Identifieur interne : 002F81 ( Main/Exploration ); précédent : 002F80; suivant : 002F82Thiopurine analogues inhibit papain-like protease of severe acute respiratory syndrome coronavirus.
Auteurs : Chi-Yuan Chou [République populaire de Chine] ; Chia-Hui Chien ; Yu-San Han ; Mojca Trstenjak Prebanda ; Hsing-Pang Hsieh ; Boris Turk ; Gu-Gang Chang ; Xin ChenSource :
- Biochemical pharmacology [ 1873-2968 ] ; 2008.
Descripteurs français
- KwdFr :
- MESH :
- antagonistes et inhibiteurs : Protéines virales.
- enzymologie : Virus du SRAS.
- Cysteine endopeptidases, Inhibiteurs de protéases, Protéines virales, Tioguanine.
English descriptors
- KwdEn :
- MESH :
- chemical , antagonists & inhibitors : Viral Proteins.
- chemical , chemistry : Cysteine Endopeptidases, Mercaptopurine, Protease Inhibitors, Thioguanine, Viral Proteins.
- enzymology : SARS Virus.
Abstract
The papain-like protease of severe acute respiratory syndrome coronavirus (PLpro) (EC 3.4.22.46) is essential for the viral life cycle and therefore represents an important antiviral target. We have identified 6MP and 6TG as reversible and slow-binding inhibitors of SARS-CoV PLpro, which is the first report about small molecule reversible inhibitors of PLpro. The inhibition mechanism was investigated by kinetic measurements and computer docking. Both compounds are competitive, selective, and reversible inhibitors of the PLpro with K(is) values approximately 10 to 20 microM. A structure-function relationship study has identified the thiocarbonyl moiety of 6MP or 6TG as the active pharmacophore essential for these inhibitions, which has not been reported before. The inhibition is selective because these compounds do not exert significant inhibitory effects against other cysteine proteases, including SARS-CoV 3CLpro and several cathepsins. Thus, our results present the first potential chemical leads against SARS-CoV PLpro, which might be used as lead compounds for further optimization to enhance their potency against SARS-CoV. Both 6MP and 6TG are still used extensively in clinics, especially for children with acute lymphoblastic or myeloblastic leukemia. In light of the possible inhibition against subset of cysteine proteases, our study has emphasized the importance to study in depth these drug actions in vivo.
DOI: 10.1016/j.bcp.2008.01.005
PubMed: 18313035
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 001C00
- to stream PubMed, to step Curation: 001C00
- to stream PubMed, to step Checkpoint: 001980
- to stream Ncbi, to step Merge: 001B91
- to stream Ncbi, to step Curation: 001B91
- to stream Ncbi, to step Checkpoint: 001B91
- to stream Main, to step Merge: 003046
- to stream Main, to step Curation: 002F81
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Thiopurine analogues inhibit papain-like protease of severe acute respiratory syndrome coronavirus.</title><author><name sortKey="Chou, Chi Yuan" sort="Chou, Chi Yuan" uniqKey="Chou C" first="Chi-Yuan" last="Chou">Chi-Yuan Chou</name><affiliation wicri:level="1"><nlm:affiliation>Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan, ROC.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan</wicri:regionArea><wicri:noRegion>Taiwan</wicri:noRegion></affiliation></author><author><name sortKey="Chien, Chia Hui" sort="Chien, Chia Hui" uniqKey="Chien C" first="Chia-Hui" last="Chien">Chia-Hui Chien</name></author><author><name sortKey="Han, Yu San" sort="Han, Yu San" uniqKey="Han Y" first="Yu-San" last="Han">Yu-San Han</name></author><author><name sortKey="Prebanda, Mojca Trstenjak" sort="Prebanda, Mojca Trstenjak" uniqKey="Prebanda M" first="Mojca Trstenjak" last="Prebanda">Mojca Trstenjak Prebanda</name></author><author><name sortKey="Hsieh, Hsing Pang" sort="Hsieh, Hsing Pang" uniqKey="Hsieh H" first="Hsing-Pang" last="Hsieh">Hsing-Pang Hsieh</name></author><author><name sortKey="Turk, Boris" sort="Turk, Boris" uniqKey="Turk B" first="Boris" last="Turk">Boris Turk</name></author><author><name sortKey="Chang, Gu Gang" sort="Chang, Gu Gang" uniqKey="Chang G" first="Gu-Gang" last="Chang">Gu-Gang Chang</name></author><author><name sortKey="Chen, Xin" sort="Chen, Xin" uniqKey="Chen X" first="Xin" last="Chen">Xin Chen</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2008">2008</date><idno type="RBID">pubmed:18313035</idno><idno type="pmid">18313035</idno><idno type="doi">10.1016/j.bcp.2008.01.005</idno><idno type="wicri:Area/PubMed/Corpus">001C00</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001C00</idno><idno type="wicri:Area/PubMed/Curation">001C00</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001C00</idno><idno type="wicri:Area/PubMed/Checkpoint">001980</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001980</idno><idno type="wicri:Area/Ncbi/Merge">001B91</idno><idno type="wicri:Area/Ncbi/Curation">001B91</idno><idno type="wicri:Area/Ncbi/Checkpoint">001B91</idno><idno type="wicri:Area/Main/Merge">003046</idno><idno type="wicri:Area/Main/Curation">002F81</idno><idno type="wicri:Area/Main/Exploration">002F81</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Thiopurine analogues inhibit papain-like protease of severe acute respiratory syndrome coronavirus.</title><author><name sortKey="Chou, Chi Yuan" sort="Chou, Chi Yuan" uniqKey="Chou C" first="Chi-Yuan" last="Chou">Chi-Yuan Chou</name><affiliation wicri:level="1"><nlm:affiliation>Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan, ROC.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan</wicri:regionArea><wicri:noRegion>Taiwan</wicri:noRegion></affiliation></author><author><name sortKey="Chien, Chia Hui" sort="Chien, Chia Hui" uniqKey="Chien C" first="Chia-Hui" last="Chien">Chia-Hui Chien</name></author><author><name sortKey="Han, Yu San" sort="Han, Yu San" uniqKey="Han Y" first="Yu-San" last="Han">Yu-San Han</name></author><author><name sortKey="Prebanda, Mojca Trstenjak" sort="Prebanda, Mojca Trstenjak" uniqKey="Prebanda M" first="Mojca Trstenjak" last="Prebanda">Mojca Trstenjak Prebanda</name></author><author><name sortKey="Hsieh, Hsing Pang" sort="Hsieh, Hsing Pang" uniqKey="Hsieh H" first="Hsing-Pang" last="Hsieh">Hsing-Pang Hsieh</name></author><author><name sortKey="Turk, Boris" sort="Turk, Boris" uniqKey="Turk B" first="Boris" last="Turk">Boris Turk</name></author><author><name sortKey="Chang, Gu Gang" sort="Chang, Gu Gang" uniqKey="Chang G" first="Gu-Gang" last="Chang">Gu-Gang Chang</name></author><author><name sortKey="Chen, Xin" sort="Chen, Xin" uniqKey="Chen X" first="Xin" last="Chen">Xin Chen</name></author></analytic><series><title level="j">Biochemical pharmacology</title><idno type="eISSN">1873-2968</idno><imprint><date when="2008" type="published">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cysteine Endopeptidases (chemistry)</term><term>Mercaptopurine (chemistry)</term><term>Protease Inhibitors (chemistry)</term><term>SARS Virus (enzymology)</term><term>Thioguanine (chemistry)</term><term>Viral Proteins (antagonists & inhibitors)</term><term>Viral Proteins (chemistry)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Cysteine endopeptidases ()</term><term>Inhibiteurs de protéases ()</term><term>Protéines virales ()</term><term>Protéines virales (antagonistes et inhibiteurs)</term><term>Tioguanine ()</term><term>Virus du SRAS (enzymologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Cysteine Endopeptidases</term><term>Mercaptopurine</term><term>Protease Inhibitors</term><term>Thioguanine</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Protéines virales</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cysteine endopeptidases</term><term>Inhibiteurs de protéases</term><term>Protéines virales</term><term>Tioguanine</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The papain-like protease of severe acute respiratory syndrome coronavirus (PLpro) (EC 3.4.22.46) is essential for the viral life cycle and therefore represents an important antiviral target. We have identified 6MP and 6TG as reversible and slow-binding inhibitors of SARS-CoV PLpro, which is the first report about small molecule reversible inhibitors of PLpro. The inhibition mechanism was investigated by kinetic measurements and computer docking. Both compounds are competitive, selective, and reversible inhibitors of the PLpro with K(is) values approximately 10 to 20 microM. A structure-function relationship study has identified the thiocarbonyl moiety of 6MP or 6TG as the active pharmacophore essential for these inhibitions, which has not been reported before. The inhibition is selective because these compounds do not exert significant inhibitory effects against other cysteine proteases, including SARS-CoV 3CLpro and several cathepsins. Thus, our results present the first potential chemical leads against SARS-CoV PLpro, which might be used as lead compounds for further optimization to enhance their potency against SARS-CoV. Both 6MP and 6TG are still used extensively in clinics, especially for children with acute lymphoblastic or myeloblastic leukemia. In light of the possible inhibition against subset of cysteine proteases, our study has emphasized the importance to study in depth these drug actions in vivo.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><noCountry><name sortKey="Chang, Gu Gang" sort="Chang, Gu Gang" uniqKey="Chang G" first="Gu-Gang" last="Chang">Gu-Gang Chang</name><name sortKey="Chen, Xin" sort="Chen, Xin" uniqKey="Chen X" first="Xin" last="Chen">Xin Chen</name><name sortKey="Chien, Chia Hui" sort="Chien, Chia Hui" uniqKey="Chien C" first="Chia-Hui" last="Chien">Chia-Hui Chien</name><name sortKey="Han, Yu San" sort="Han, Yu San" uniqKey="Han Y" first="Yu-San" last="Han">Yu-San Han</name><name sortKey="Hsieh, Hsing Pang" sort="Hsieh, Hsing Pang" uniqKey="Hsieh H" first="Hsing-Pang" last="Hsieh">Hsing-Pang Hsieh</name><name sortKey="Prebanda, Mojca Trstenjak" sort="Prebanda, Mojca Trstenjak" uniqKey="Prebanda M" first="Mojca Trstenjak" last="Prebanda">Mojca Trstenjak Prebanda</name><name sortKey="Turk, Boris" sort="Turk, Boris" uniqKey="Turk B" first="Boris" last="Turk">Boris Turk</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Chou, Chi Yuan" sort="Chou, Chi Yuan" uniqKey="Chou C" first="Chi-Yuan" last="Chou">Chi-Yuan Chou</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002F81 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 002F81 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= SrasV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:18313035
|texte= Thiopurine analogues inhibit papain-like protease of severe acute respiratory syndrome coronavirus.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:18313035" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a SrasV1
| This area was generated with Dilib version V0.6.33. |  |