Human coronavirus OC43 3CL protease and the potential of ML188 as a broad-spectrum lead compound: homology modelling and molecular dynamic studies.
Identifieur interne : 001307 ( Main/Exploration ); précédent : 001306; suivant : 001308Human coronavirus OC43 3CL protease and the potential of ML188 as a broad-spectrum lead compound: homology modelling and molecular dynamic studies.
Auteurs : Michael Berry [Afrique du Sud] ; Burtram Fielding [Afrique du Sud] ; Junaid Gamieldien [Afrique du Sud]Source :
- BMC structural biology [ 1472-6807 ] ; 2015.
Descripteurs français
- KwdFr :
- Acétamides (pharmacologie), Coronavirus humain OC43 (), Coronavirus humain OC43 (enzymologie), Cysteine endopeptidases (), Cysteine endopeptidases (métabolisme), Domaine catalytique, Humains, Modèles moléculaires, Protéines virales (), Protéines virales (antagonistes et inhibiteurs), Relation structure-activité, Similitude structurale de protéines, Simulation de dynamique moléculaire, Structure tertiaire des protéines.
- MESH :
- antagonistes et inhibiteurs : Protéines virales.
- enzymologie : Coronavirus humain OC43.
- métabolisme : Cysteine endopeptidases.
- pharmacologie : Acétamides.
- Coronavirus humain OC43, Cysteine endopeptidases, Domaine catalytique, Humains, Modèles moléculaires, Protéines virales, Relation structure-activité, Similitude structurale de protéines, Simulation de dynamique moléculaire, Structure tertiaire des protéines.
English descriptors
- KwdEn :
- Acetamides (pharmacology), Catalytic Domain, Coronavirus OC43, Human (chemistry), Coronavirus OC43, Human (enzymology), Cysteine Endopeptidases (chemistry), Cysteine Endopeptidases (metabolism), Humans, Models, Molecular, Molecular Dynamics Simulation, Protein Structure, Tertiary, Structural Homology, Protein, Structure-Activity Relationship, Viral Proteins (antagonists & inhibitors), Viral Proteins (chemistry).
- MESH :
- chemical , antagonists & inhibitors : Viral Proteins.
- chemical , chemistry : Cysteine Endopeptidases, Viral Proteins.
- chemical , metabolism : Cysteine Endopeptidases.
- chemical , pharmacology : Acetamides.
- chemistry : Coronavirus OC43, Human.
- enzymology : Coronavirus OC43, Human.
- Catalytic Domain, Humans, Models, Molecular, Molecular Dynamics Simulation, Protein Structure, Tertiary, Structural Homology, Protein, Structure-Activity Relationship.
Abstract
The coronavirus 3 chymotrypsin-like protease (3CL(pro)) is a validated target in the design of potential anticoronavirus inhibitors. The high degree of homology within the protease's active site and substrate conservation supports the identification of broad spectrum lead compounds. A previous study identified the compound ML188, also termed 16R, as an inhibitor of the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) 3CL(pro). This study will detail the generation of a homology model of the 3CL(pro) of the human coronavirus OC43 and determine the potential of 16R to form a broad-spectrum lead compound. MODELLER was used to generate a suitable three-dimensional model of the OC43 3CL(pro) and the Prime module of Schrӧdinger predicted the binding conformation and free energy of binding of 16R within the 3CL(pro) active site. Molecular dynamics further confirmed ligand stability and hydrogen bonding networks.
DOI: 10.1186/s12900-015-0035-3
PubMed: 25928480
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000E24
- to stream PubMed, to step Curation: 000E24
- to stream PubMed, to step Checkpoint: 000E09
- to stream Ncbi, to step Merge: 002A68
- to stream Ncbi, to step Curation: 002A68
- to stream Ncbi, to step Checkpoint: 002A68
- to stream Main, to step Merge: 001309
- to stream Main, to step Curation: 001307
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Human coronavirus OC43 3CL protease and the potential of ML188 as a broad-spectrum lead compound: homology modelling and molecular dynamic studies.</title><author><name sortKey="Berry, Michael" sort="Berry, Michael" uniqKey="Berry M" first="Michael" last="Berry">Michael Berry</name><affiliation wicri:level="1"><nlm:affiliation>South African National Bioinformatics Institute/ MRC Unit for Bioinformatics Capacity Development, University of the Western Cape, Bellville, South Africa. michael@sanbi.ac.za.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>South African National Bioinformatics Institute/ MRC Unit for Bioinformatics Capacity Development, University of the Western Cape, Bellville</wicri:regionArea><wicri:noRegion>Bellville</wicri:noRegion></affiliation></author><author><name sortKey="Fielding, Burtram" sort="Fielding, Burtram" uniqKey="Fielding B" first="Burtram" last="Fielding">Burtram Fielding</name><affiliation wicri:level="1"><nlm:affiliation>Molecular Biology and Virology Laboratory, Department of Medical Biosciences, University of the Western Cape, Bellville, South Africa. bfielding@uwc.ac.za.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Molecular Biology and Virology Laboratory, Department of Medical Biosciences, University of the Western Cape, Bellville</wicri:regionArea><wicri:noRegion>Bellville</wicri:noRegion></affiliation></author><author><name sortKey="Gamieldien, Junaid" sort="Gamieldien, Junaid" uniqKey="Gamieldien J" first="Junaid" last="Gamieldien">Junaid Gamieldien</name><affiliation wicri:level="1"><nlm:affiliation>South African National Bioinformatics Institute/ MRC Unit for Bioinformatics Capacity Development, University of the Western Cape, Bellville, South Africa. junaid@sanbi.ac.za.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>South African National Bioinformatics Institute/ MRC Unit for Bioinformatics Capacity Development, University of the Western Cape, Bellville</wicri:regionArea><wicri:noRegion>Bellville</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:25928480</idno><idno type="pmid">25928480</idno><idno type="doi">10.1186/s12900-015-0035-3</idno><idno type="wicri:Area/PubMed/Corpus">000E24</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000E24</idno><idno type="wicri:Area/PubMed/Curation">000E24</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000E24</idno><idno type="wicri:Area/PubMed/Checkpoint">000E09</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000E09</idno><idno type="wicri:Area/Ncbi/Merge">002A68</idno><idno type="wicri:Area/Ncbi/Curation">002A68</idno><idno type="wicri:Area/Ncbi/Checkpoint">002A68</idno><idno type="wicri:Area/Main/Merge">001309</idno><idno type="wicri:Area/Main/Curation">001307</idno><idno type="wicri:Area/Main/Exploration">001307</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Human coronavirus OC43 3CL protease and the potential of ML188 as a broad-spectrum lead compound: homology modelling and molecular dynamic studies.</title><author><name sortKey="Berry, Michael" sort="Berry, Michael" uniqKey="Berry M" first="Michael" last="Berry">Michael Berry</name><affiliation wicri:level="1"><nlm:affiliation>South African National Bioinformatics Institute/ MRC Unit for Bioinformatics Capacity Development, University of the Western Cape, Bellville, South Africa. michael@sanbi.ac.za.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>South African National Bioinformatics Institute/ MRC Unit for Bioinformatics Capacity Development, University of the Western Cape, Bellville</wicri:regionArea><wicri:noRegion>Bellville</wicri:noRegion></affiliation></author><author><name sortKey="Fielding, Burtram" sort="Fielding, Burtram" uniqKey="Fielding B" first="Burtram" last="Fielding">Burtram Fielding</name><affiliation wicri:level="1"><nlm:affiliation>Molecular Biology and Virology Laboratory, Department of Medical Biosciences, University of the Western Cape, Bellville, South Africa. bfielding@uwc.ac.za.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Molecular Biology and Virology Laboratory, Department of Medical Biosciences, University of the Western Cape, Bellville</wicri:regionArea><wicri:noRegion>Bellville</wicri:noRegion></affiliation></author><author><name sortKey="Gamieldien, Junaid" sort="Gamieldien, Junaid" uniqKey="Gamieldien J" first="Junaid" last="Gamieldien">Junaid Gamieldien</name><affiliation wicri:level="1"><nlm:affiliation>South African National Bioinformatics Institute/ MRC Unit for Bioinformatics Capacity Development, University of the Western Cape, Bellville, South Africa. junaid@sanbi.ac.za.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>South African National Bioinformatics Institute/ MRC Unit for Bioinformatics Capacity Development, University of the Western Cape, Bellville</wicri:regionArea><wicri:noRegion>Bellville</wicri:noRegion></affiliation></author></analytic><series><title level="j">BMC structural biology</title><idno type="eISSN">1472-6807</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acetamides (pharmacology)</term><term>Catalytic Domain</term><term>Coronavirus OC43, Human (chemistry)</term><term>Coronavirus OC43, Human (enzymology)</term><term>Cysteine Endopeptidases (chemistry)</term><term>Cysteine Endopeptidases (metabolism)</term><term>Humans</term><term>Models, Molecular</term><term>Molecular Dynamics Simulation</term><term>Protein Structure, Tertiary</term><term>Structural Homology, Protein</term><term>Structure-Activity Relationship</term><term>Viral Proteins (antagonists & inhibitors)</term><term>Viral Proteins (chemistry)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acétamides (pharmacologie)</term><term>Coronavirus humain OC43 ()</term><term>Coronavirus humain OC43 (enzymologie)</term><term>Cysteine endopeptidases ()</term><term>Cysteine endopeptidases (métabolisme)</term><term>Domaine catalytique</term><term>Humains</term><term>Modèles moléculaires</term><term>Protéines virales ()</term><term>Protéines virales (antagonistes et inhibiteurs)</term><term>Relation structure-activité</term><term>Similitude structurale de protéines</term><term>Simulation de dynamique moléculaire</term><term>Structure tertiaire des protéines</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>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cysteine Endopeptidases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Acetamides</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Protéines virales</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Coronavirus OC43, Human</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Coronavirus humain OC43</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Coronavirus OC43, Human</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cysteine endopeptidases</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Acétamides</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Catalytic Domain</term><term>Humans</term><term>Models, Molecular</term><term>Molecular Dynamics Simulation</term><term>Protein Structure, Tertiary</term><term>Structural Homology, Protein</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Coronavirus humain OC43</term><term>Cysteine endopeptidases</term><term>Domaine catalytique</term><term>Humains</term><term>Modèles moléculaires</term><term>Protéines virales</term><term>Relation structure-activité</term><term>Similitude structurale de protéines</term><term>Simulation de dynamique moléculaire</term><term>Structure tertiaire des protéines</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The coronavirus 3 chymotrypsin-like protease (3CL(pro)) is a validated target in the design of potential anticoronavirus inhibitors. The high degree of homology within the protease's active site and substrate conservation supports the identification of broad spectrum lead compounds. A previous study identified the compound ML188, also termed 16R, as an inhibitor of the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) 3CL(pro). This study will detail the generation of a homology model of the 3CL(pro) of the human coronavirus OC43 and determine the potential of 16R to form a broad-spectrum lead compound. MODELLER was used to generate a suitable three-dimensional model of the OC43 3CL(pro) and the Prime module of Schrӧdinger predicted the binding conformation and free energy of binding of 16R within the 3CL(pro) active site. Molecular dynamics further confirmed ligand stability and hydrogen bonding networks.</div></front></TEI><affiliations><list><country><li>Afrique du Sud</li></country></list><tree><country name="Afrique du Sud"><noRegion><name sortKey="Berry, Michael" sort="Berry, Michael" uniqKey="Berry M" first="Michael" last="Berry">Michael Berry</name></noRegion><name sortKey="Fielding, Burtram" sort="Fielding, Burtram" uniqKey="Fielding B" first="Burtram" last="Fielding">Burtram Fielding</name><name sortKey="Gamieldien, Junaid" sort="Gamieldien, Junaid" uniqKey="Gamieldien J" first="Junaid" last="Gamieldien">Junaid Gamieldien</name></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 001307 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001307 | 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:25928480
|texte= Human coronavirus OC43 3CL protease and the potential of ML188 as a broad-spectrum lead compound: homology modelling and molecular dynamic studies.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:25928480" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a SrasV1
| This area was generated with Dilib version V0.6.33. |  |