SrasV1, Main, Merge, bibRecord, 002035

Virtual screening identification of novel severe acute respiratory syndrome 3C-like protease inhibitors and in vitro confirmation.

Identifieur interne : 002035 ( Main/Merge ); précédent : 002034; suivant : 002036

Virtual screening identification of novel severe acute respiratory syndrome 3C-like protease inhibitors and in vitro confirmation.

Auteurs : Thi Thanh Hanh Nguyen [Corée du Sud] ; Hwa-Ja Ryu ; Se-Hoon Lee ; Soonwook Hwang ; Vincent Breton ; Joon Haeng Rhee ; Doman Kim

Source :

Bioorganic & medicinal chemistry letters [ 1464-3405 ] ; 2011.

RBID : pubmed:21470860

Descripteurs français

KwdFr :
- Activation enzymatique (), Bibliothèques de petites molécules, Concentration inhibitrice 50, Cysteine endopeptidases (génétique), Escherichia coli (génétique), Escherichia coli (métabolisme), Fixation compétitive, Inhibiteurs de protéases (), Inhibiteurs de protéases (pharmacologie), Modèles moléculaires, Protéines recombinantes (), Protéines recombinantes (génétique), Protéines virales (antagonistes et inhibiteurs), Protéines virales (génétique), Simulation numérique, Structure moléculaire, Systèmes de délivrance de médicaments, Virus du SRAS (), Virus du SRAS (enzymologie).
MESH :
- antagonistes et inhibiteurs : Protéines virales.
- enzymologie : Virus du SRAS.
- génétique : Cysteine endopeptidases, Escherichia coli, Protéines recombinantes, Protéines virales.
- métabolisme : Escherichia coli.
- pharmacologie : Inhibiteurs de protéases.
- Activation enzymatique, Bibliothèques de petites molécules, Concentration inhibitrice 50, Fixation compétitive, Inhibiteurs de protéases, Modèles moléculaires, Protéines recombinantes, Simulation numérique, Structure moléculaire, Systèmes de délivrance de médicaments, Virus du SRAS.

English descriptors

KwdEn :
- Binding, Competitive, Computer Simulation, Cysteine Endopeptidases (genetics), Drug Delivery Systems, Enzyme Activation (drug effects), Escherichia coli (genetics), Escherichia coli (metabolism), Inhibitory Concentration 50, Models, Molecular, Molecular Structure, Protease Inhibitors (chemistry), Protease Inhibitors (pharmacology), Recombinant Proteins (chemistry), Recombinant Proteins (genetics), SARS Virus (drug effects), SARS Virus (enzymology), Small Molecule Libraries, Viral Proteins (antagonists & inhibitors), Viral Proteins (genetics).
MESH :
- chemical , antagonists & inhibitors : Viral Proteins.
- chemical , chemistry : Protease Inhibitors, Recombinant Proteins.
- chemical , genetics : Cysteine Endopeptidases, Recombinant Proteins, Viral Proteins.
- drug effects : Enzyme Activation, SARS Virus.
- enzymology : SARS Virus.
- genetics : Escherichia coli.
- metabolism : Escherichia coli.
- chemical , pharmacology : Protease Inhibitors.
- Binding, Competitive, Computer Simulation, Drug Delivery Systems, Inhibitory Concentration 50, Models, Molecular, Molecular Structure, Small Molecule Libraries.
mix :
- 3CL Protease, Autodock, Coronavirus, FRET-based assays, Grid, SARS, Severe acute respiratory syndrome, Virtual screening.

Abstract

The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is vital for SARS-CoV replication and is a promising drug target. Structure based virtual screening of 308307 chemical compounds was performed using the computation tool Autodock 3.0.5 on a WISDOM Production Environment. The top 1468 ranked compounds with free binding energy ranging from -14.0 to -17.09 kcal mol(-1) were selected to check the hydrogen bond interaction with amino acid residues in the active site of 3CL(pro). Fifty-three compounds from 35 main groups were tested in an in vitro assay for inhibition of 3CL(pro) expressed by Escherichia coli. Seven of the 53 compounds were selected; their IC(50) ranged from 38.57±2.41 to 101.38±3.27 μM. Two strong 3CL(pro) inhibitors were further identified as competitive inhibitors of 3CL(pro) with K(i) values of 9.11±1.6 and 9.93±0.44 μM. Hydrophobic and hydrogen bond interactions of compound with amino acid residues in the active site of 3CL(pro) were also identified.

Url:

http://hal.in2p3.fr/in2p3-00586373

DOI: 10.1016/j.bmcl.2011.03.034
PubMed: 21470860

Links to Exploration step

pubmed:21470860

Le document en format XML

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<front><div type="abstract" xml:lang="en">The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is vital for SARS-CoV replication and is a promising drug target. Structure based virtual screening of 308307 chemical compounds was performed using the computation tool Autodock 3.0.5 on a WISDOM Production Environment. The top 1468 ranked compounds with free binding energy ranging from -14.0 to -17.09 kcal mol(-1) were selected to check the hydrogen bond interaction with amino acid residues in the active site of 3CL(pro). Fifty-three compounds from 35 main groups were tested in an in vitro assay for inhibition of 3CL(pro) expressed by Escherichia coli. Seven of the 53 compounds were selected; their IC(50) ranged from 38.57±2.41 to 101.38±3.27 μM. Two strong 3CL(pro) inhibitors were further identified as competitive inhibitors of 3CL(pro) with K(i) values of 9.11±1.6 and 9.93±0.44 μM. Hydrophobic and hydrogen bond interactions of compound with amino acid residues in the active site of 3CL(pro) were also identified.</div>
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<front><div type="abstract" xml:lang="en">              <p>The 3C-like protease (3CLpro) of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is vital for SARS-CoV replication and is a promising drug target. Structure based virtual screening of 308 307 chemical compounds was performed using the computation tool Autodock 3.0.5 on a WISDOM Production Environment. The top 1468 ranked compounds with free binding energy ranging from -14.0 to -17.09 kcal mol-1 were selected to check the hydrogen bond interaction with amino acid residues in the active site of 3CLpro. Fifty-three compounds from 35 main groups were tested in an in vitro assay for inhibition of 3CLpro expressed by Escherichia coli. Seven of the 53 compounds were selected; their IC50 ranged from 38.57 ± 2.41 to 101.38 ± 3.27 muM. Two strong 3CLpro inhibitors were further identified as competitive inhibitors of 3CLpro with Ki values of 9.11 ± 1.6 and 9.93 ± 0.44 muM. Hydrophobic and hydrogen bond interactions of compound with amino acid residues in the active site of 3CLpro were also identified.</p>
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<PubMed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Virtual screening identification of novel severe acute respiratory syndrome 3C-like protease inhibitors and in vitro confirmation.</title>
<author><name sortKey="Nguyen, Thi Thanh Hanh" sort="Nguyen, Thi Thanh Hanh" uniqKey="Nguyen T" first="Thi Thanh Hanh" last="Nguyen">Thi Thanh Hanh Nguyen</name>
<affiliation wicri:level="1"><nlm:affiliation>School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.</nlm:affiliation>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>School of Biological Sciences and Technology, Chonnam National University, Gwangju</wicri:regionArea>
<wicri:noRegion>Gwangju</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ryu, Hwa Ja" sort="Ryu, Hwa Ja" uniqKey="Ryu H" first="Hwa-Ja" last="Ryu">Hwa-Ja Ryu</name>
</author>
<author><name sortKey="Lee, Se Hoon" sort="Lee, Se Hoon" uniqKey="Lee S" first="Se-Hoon" last="Lee">Se-Hoon Lee</name>
</author>
<author><name sortKey="Hwang, Soonwook" sort="Hwang, Soonwook" uniqKey="Hwang S" first="Soonwook" last="Hwang">Soonwook Hwang</name>
</author>
<author><name sortKey="Breton, Vincent" sort="Breton, Vincent" uniqKey="Breton V" first="Vincent" last="Breton">Vincent Breton</name>
</author>
<author><name sortKey="Rhee, Joon Haeng" sort="Rhee, Joon Haeng" uniqKey="Rhee J" first="Joon Haeng" last="Rhee">Joon Haeng Rhee</name>
</author>
<author><name sortKey="Kim, Doman" sort="Kim, Doman" uniqKey="Kim D" first="Doman" last="Kim">Doman Kim</name>
</author>
</titleStmt>
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<date when="2011">2011</date>
<idno type="RBID">pubmed:21470860</idno>
<idno type="pmid">21470860</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Virtual screening identification of novel severe acute respiratory syndrome 3C-like protease inhibitors and in vitro confirmation.</title>
<author><name sortKey="Nguyen, Thi Thanh Hanh" sort="Nguyen, Thi Thanh Hanh" uniqKey="Nguyen T" first="Thi Thanh Hanh" last="Nguyen">Thi Thanh Hanh Nguyen</name>
<affiliation wicri:level="1"><nlm:affiliation>School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.</nlm:affiliation>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>School of Biological Sciences and Technology, Chonnam National University, Gwangju</wicri:regionArea>
<wicri:noRegion>Gwangju</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ryu, Hwa Ja" sort="Ryu, Hwa Ja" uniqKey="Ryu H" first="Hwa-Ja" last="Ryu">Hwa-Ja Ryu</name>
</author>
<author><name sortKey="Lee, Se Hoon" sort="Lee, Se Hoon" uniqKey="Lee S" first="Se-Hoon" last="Lee">Se-Hoon Lee</name>
</author>
<author><name sortKey="Hwang, Soonwook" sort="Hwang, Soonwook" uniqKey="Hwang S" first="Soonwook" last="Hwang">Soonwook Hwang</name>
</author>
<author><name sortKey="Breton, Vincent" sort="Breton, Vincent" uniqKey="Breton V" first="Vincent" last="Breton">Vincent Breton</name>
</author>
<author><name sortKey="Rhee, Joon Haeng" sort="Rhee, Joon Haeng" uniqKey="Rhee J" first="Joon Haeng" last="Rhee">Joon Haeng Rhee</name>
</author>
<author><name sortKey="Kim, Doman" sort="Kim, Doman" uniqKey="Kim D" first="Doman" last="Kim">Doman Kim</name>
</author>
</analytic>
<series><title level="j">Bioorganic & medicinal chemistry letters</title>
<idno type="eISSN">1464-3405</idno>
<imprint><date when="2011" type="published">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Binding, Competitive</term>
<term>Computer Simulation</term>
<term>Cysteine Endopeptidases (genetics)</term>
<term>Drug Delivery Systems</term>
<term>Enzyme Activation (drug effects)</term>
<term>Escherichia coli (genetics)</term>
<term>Escherichia coli (metabolism)</term>
<term>Inhibitory Concentration 50</term>
<term>Models, Molecular</term>
<term>Molecular Structure</term>
<term>Protease Inhibitors (chemistry)</term>
<term>Protease Inhibitors (pharmacology)</term>
<term>Recombinant Proteins (chemistry)</term>
<term>Recombinant Proteins (genetics)</term>
<term>SARS Virus (drug effects)</term>
<term>SARS Virus (enzymology)</term>
<term>Small Molecule Libraries</term>
<term>Viral Proteins (antagonists & inhibitors)</term>
<term>Viral Proteins (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Activation enzymatique ()</term>
<term>Bibliothèques de petites molécules</term>
<term>Concentration inhibitrice 50</term>
<term>Cysteine endopeptidases (génétique)</term>
<term>Escherichia coli (génétique)</term>
<term>Escherichia coli (métabolisme)</term>
<term>Fixation compétitive</term>
<term>Inhibiteurs de protéases ()</term>
<term>Inhibiteurs de protéases (pharmacologie)</term>
<term>Modèles moléculaires</term>
<term>Protéines recombinantes ()</term>
<term>Protéines recombinantes (génétique)</term>
<term>Protéines virales (antagonistes et inhibiteurs)</term>
<term>Protéines virales (génétique)</term>
<term>Simulation numérique</term>
<term>Structure moléculaire</term>
<term>Systèmes de délivrance de médicaments</term>
<term>Virus du SRAS ()</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>Protease Inhibitors</term>
<term>Recombinant Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cysteine Endopeptidases</term>
<term>Recombinant Proteins</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="drug effects" xml:lang="en"><term>Enzyme Activation</term>
<term>SARS Virus</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" qualifier="genetics" xml:lang="en"><term>Escherichia coli</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Cysteine endopeptidases</term>
<term>Escherichia coli</term>
<term>Protéines recombinantes</term>
<term>Protéines virales</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Escherichia coli</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Escherichia coli</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Inhibiteurs de protéases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Protease Inhibitors</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Binding, Competitive</term>
<term>Computer Simulation</term>
<term>Drug Delivery Systems</term>
<term>Inhibitory Concentration 50</term>
<term>Models, Molecular</term>
<term>Molecular Structure</term>
<term>Small Molecule Libraries</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Activation enzymatique</term>
<term>Bibliothèques de petites molécules</term>
<term>Concentration inhibitrice 50</term>
<term>Fixation compétitive</term>
<term>Inhibiteurs de protéases</term>
<term>Modèles moléculaires</term>
<term>Protéines recombinantes</term>
<term>Simulation numérique</term>
<term>Structure moléculaire</term>
<term>Systèmes de délivrance de médicaments</term>
<term>Virus du SRAS</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is vital for SARS-CoV replication and is a promising drug target. Structure based virtual screening of 308307 chemical compounds was performed using the computation tool Autodock 3.0.5 on a WISDOM Production Environment. The top 1468 ranked compounds with free binding energy ranging from -14.0 to -17.09 kcal mol(-1) were selected to check the hydrogen bond interaction with amino acid residues in the active site of 3CL(pro). Fifty-three compounds from 35 main groups were tested in an in vitro assay for inhibition of 3CL(pro) expressed by Escherichia coli. Seven of the 53 compounds were selected; their IC(50) ranged from 38.57±2.41 to 101.38±3.27 μM. Two strong 3CL(pro) inhibitors were further identified as competitive inhibitors of 3CL(pro) with K(i) values of 9.11±1.6 and 9.93±0.44 μM. Hydrophobic and hydrogen bond interactions of compound with amino acid residues in the active site of 3CL(pro) were also identified.</div>
</front>
</TEI>
</PubMed>
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Virtual screening identification of novel severe acute respiratory syndrome 3C-like protease inhibitors and in vitro confirmation.

Virtual screening identification of novel severe acute respiratory syndrome 3C-like protease inhibitors and in vitro confirmation.

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