Severe Acute Respiratory Syndrome Coronavirus Replication Inhibitor That Interferes with the Nucleic Acid Unwinding of the Viral Helicase
Identifieur interne : 000038 ( PascalFrancis/Checkpoint ); précédent : 000037; suivant : 000039Severe Acute Respiratory Syndrome Coronavirus Replication Inhibitor That Interferes with the Nucleic Acid Unwinding of the Viral Helicase
Auteurs : Adeyemi O. Adedeji [États-Unis] ; Kamalendra Singh [États-Unis] ; Nicholas E. Calcaterra [États-Unis] ; Marta L. Dediego [Espagne] ; Luis Enjuanes [Espagne] ; Susan Weiss [États-Unis] ; Stefan G. Sarafianos [États-Unis]Source :
- Antimicrobial agents and chemotherapy [ 0066-4804 ] ; 2012.
Descripteurs français
- Pascal (Inist)
English descriptors
Abstract
Severe acute respiratory syndrome (SARS) is a highly contagious disease, caused by SARS coronavirus (SARS-CoV), for which there are no approved treatments. We report the discovery of a potent inhibitor of SARS-CoV that blocks replication by inhibiting the unwinding activity of the SARS-CoV helicase (nsp13). We used a Förster resonance energy transfer (FRET)-based helicase assay to screen the Maybridge Hitfinder chemical library. We identified and validated a compound (SSYA10-001) that specifically blocks the double-stranded RNA (dsRNA) and dsDNA unwinding activities of nsp13, with 50% inhibitory concentrations (IC50s) of 5.70 and 5.30 μM, respectively. This compound also has inhibitory activity (50% effective concentration [EC50] = 8.95 μM) in a SARS-CoV replicon assay, with low cytotoxicity (50% cytotoxic concentration [CC50] = >250 μM), suggesting that the helicase plays a still unidentified critical role in the SARS-CoV life cycle. Enzyme kinetic studies on the mechanism of nsp13 inhibition revealed that SSYA10-001 acts as a noncompetitive inhibitor of nsp13 with respect to nucleic acid and ATP substrates. Moreover, SSYA10-001 does not affect ATP hydrolysis or nsp13 binding to the nucleic acid substrate. SSYA10-001 did not inhibit hepatitis C virus (HCV) helicase, other bacterial and viral RNA-dependent RNA polymerases, or reverse transcriptase. These results suggest that SSYA10-001 specifically blocks nsp13 through a novel mechanism and is less likely to interfere with the functions of cellular enzymes that process nucleic acids or ATP. Hence, it is possible that SSYA10-001 inhibits unwinding by nsp13 by affecting conformational changes during the course of the reaction or translocation on the nucleic acid. SSYA10-001 will be a valuable tool for studying the specific role of nsp13 in the SARS-CoV life cycle, which could be a model for other nidoviruses and also a candidate for further development as a SARS antiviral target.
Affiliations:
Links toward previous steps (curation, corpus...)
Links to Exploration step
Pascal:12-0363176Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Severe Acute Respiratory Syndrome Coronavirus Replication Inhibitor That Interferes with the Nucleic Acid Unwinding of the Viral Helicase</title>
<author><name sortKey="Adedeji, Adeyemi O" sort="Adedeji, Adeyemi O" uniqKey="Adedeji A" first="Adeyemi O." last="Adedeji">Adeyemi O. Adedeji</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Christopher S. Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine</s1>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Christopher S. Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Singh, Kamalendra" sort="Singh, Kamalendra" uniqKey="Singh K" first="Kamalendra" last="Singh">Kamalendra Singh</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Christopher S. Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine</s1>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Christopher S. Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Calcaterra, Nicholas E" sort="Calcaterra, Nicholas E" uniqKey="Calcaterra N" first="Nicholas E." last="Calcaterra">Nicholas E. Calcaterra</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Christopher S. Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine</s1>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Christopher S. Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine</wicri:noRegion>
</affiliation>
<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Biochemistry, University of Missouri</s1>
<s2>Columbia, Missouri</s2>
<s3>USA</s3>
<sZ>3 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Missouri (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dediego, Marta L" sort="Dediego, Marta L" uniqKey="Dediego M" first="Marta L." last="Dediego">Marta L. Dediego</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Centro Nacional de Biotecnología-CSIC Spanish Council for Scientific Research, Campus Universidad Autónoma</s1>
<s2>Madrid</s2>
<s3>ESP</s3>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
</inist:fA14>
<country>Espagne</country>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Enjuanes, Luis" sort="Enjuanes, Luis" uniqKey="Enjuanes L" first="Luis" last="Enjuanes">Luis Enjuanes</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Centro Nacional de Biotecnología-CSIC Spanish Council for Scientific Research, Campus Universidad Autónoma</s1>
<s2>Madrid</s2>
<s3>ESP</s3>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
</inist:fA14>
<country>Espagne</country>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Weiss, Susan" sort="Weiss, Susan" uniqKey="Weiss S" first="Susan" last="Weiss">Susan Weiss</name>
<affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Department of Microbiology, University of Pennsylvania, School of Medicine</s1>
<s2>Philadelphia, Pennsylvania</s2>
<s3>USA</s3>
<sZ>6 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Sarafianos, Stefan G" sort="Sarafianos, Stefan G" uniqKey="Sarafianos S" first="Stefan G." last="Sarafianos">Stefan G. Sarafianos</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Christopher S. Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine</s1>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Christopher S. Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine</wicri:noRegion>
</affiliation>
<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Biochemistry, University of Missouri</s1>
<s2>Columbia, Missouri</s2>
<s3>USA</s3>
<sZ>3 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Missouri (État)</region>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">INIST</idno>
<idno type="inist">12-0363176</idno>
<date when="2012">2012</date>
<idno type="stanalyst">PASCAL 12-0363176 INIST</idno>
<idno type="RBID">Pascal:12-0363176</idno>
<idno type="wicri:Area/PascalFrancis/Corpus">000049</idno>
<idno type="wicri:Area/PascalFrancis/Curation">000938</idno>
<idno type="wicri:Area/PascalFrancis/Checkpoint">000038</idno>
<idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000038</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Severe Acute Respiratory Syndrome Coronavirus Replication Inhibitor That Interferes with the Nucleic Acid Unwinding of the Viral Helicase</title>
<author><name sortKey="Adedeji, Adeyemi O" sort="Adedeji, Adeyemi O" uniqKey="Adedeji A" first="Adeyemi O." last="Adedeji">Adeyemi O. Adedeji</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Christopher S. Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine</s1>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Christopher S. Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Singh, Kamalendra" sort="Singh, Kamalendra" uniqKey="Singh K" first="Kamalendra" last="Singh">Kamalendra Singh</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Christopher S. Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine</s1>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Christopher S. Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Calcaterra, Nicholas E" sort="Calcaterra, Nicholas E" uniqKey="Calcaterra N" first="Nicholas E." last="Calcaterra">Nicholas E. Calcaterra</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Christopher S. Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine</s1>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Christopher S. Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine</wicri:noRegion>
</affiliation>
<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Biochemistry, University of Missouri</s1>
<s2>Columbia, Missouri</s2>
<s3>USA</s3>
<sZ>3 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Missouri (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dediego, Marta L" sort="Dediego, Marta L" uniqKey="Dediego M" first="Marta L." last="Dediego">Marta L. Dediego</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Centro Nacional de Biotecnología-CSIC Spanish Council for Scientific Research, Campus Universidad Autónoma</s1>
<s2>Madrid</s2>
<s3>ESP</s3>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
</inist:fA14>
<country>Espagne</country>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Enjuanes, Luis" sort="Enjuanes, Luis" uniqKey="Enjuanes L" first="Luis" last="Enjuanes">Luis Enjuanes</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Centro Nacional de Biotecnología-CSIC Spanish Council for Scientific Research, Campus Universidad Autónoma</s1>
<s2>Madrid</s2>
<s3>ESP</s3>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
</inist:fA14>
<country>Espagne</country>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Weiss, Susan" sort="Weiss, Susan" uniqKey="Weiss S" first="Susan" last="Weiss">Susan Weiss</name>
<affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Department of Microbiology, University of Pennsylvania, School of Medicine</s1>
<s2>Philadelphia, Pennsylvania</s2>
<s3>USA</s3>
<sZ>6 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Sarafianos, Stefan G" sort="Sarafianos, Stefan G" uniqKey="Sarafianos S" first="Stefan G." last="Sarafianos">Stefan G. Sarafianos</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Christopher S. Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine</s1>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Christopher S. Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine</wicri:noRegion>
</affiliation>
<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Biochemistry, University of Missouri</s1>
<s2>Columbia, Missouri</s2>
<s3>USA</s3>
<sZ>3 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Missouri (État)</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Antimicrobial agents and chemotherapy</title>
<title level="j" type="abbreviated">Antimicrob. agents chemother.</title>
<idno type="ISSN">0066-4804</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Antimicrobial agents and chemotherapy</title>
<title level="j" type="abbreviated">Antimicrob. agents chemother.</title>
<idno type="ISSN">0066-4804</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Coronavirus</term>
<term>Inhibitor</term>
<term>Nucleic acid</term>
<term>Replication</term>
<term>Severe acute respiratory syndrome</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term>
<term>Coronavirus</term>
<term>Réplication</term>
<term>Inhibiteur</term>
<term>Acide nucléique</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Severe acute respiratory syndrome (SARS) is a highly contagious disease, caused by SARS coronavirus (SARS-CoV), for which there are no approved treatments. We report the discovery of a potent inhibitor of SARS-CoV that blocks replication by inhibiting the unwinding activity of the SARS-CoV helicase (nsp13). We used a Förster resonance energy transfer (FRET)-based helicase assay to screen the Maybridge Hitfinder chemical library. We identified and validated a compound (SSYA10-001) that specifically blocks the double-stranded RNA (dsRNA) and dsDNA unwinding activities of nsp13, with 50% inhibitory concentrations (IC<sub>50</sub>
s) of 5.70 and 5.30 μM, respectively. This compound also has inhibitory activity (50% effective concentration [EC<sub>50</sub>
] = 8.95 μM) in a SARS-CoV replicon assay, with low cytotoxicity (50% cytotoxic concentration [CC<sub>50</sub>
] = >250 μM), suggesting that the helicase plays a still unidentified critical role in the SARS-CoV life cycle. Enzyme kinetic studies on the mechanism of nsp13 inhibition revealed that SSYA10-001 acts as a noncompetitive inhibitor of nsp13 with respect to nucleic acid and ATP substrates. Moreover, SSYA10-001 does not affect ATP hydrolysis or nsp13 binding to the nucleic acid substrate. SSYA10-001 did not inhibit hepatitis C virus (HCV) helicase, other bacterial and viral RNA-dependent RNA polymerases, or reverse transcriptase. These results suggest that SSYA10-001 specifically blocks nsp13 through a novel mechanism and is less likely to interfere with the functions of cellular enzymes that process nucleic acids or ATP. Hence, it is possible that SSYA10-001 inhibits unwinding by nsp13 by affecting conformational changes during the course of the reaction or translocation on the nucleic acid. SSYA10-001 will be a valuable tool for studying the specific role of nsp13 in the SARS-CoV life cycle, which could be a model for other nidoviruses and also a candidate for further development as a SARS antiviral target.</div>
</front>
</TEI>
<inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0066-4804</s0>
</fA01>
<fA02 i1="01"><s0>AACHAX</s0>
</fA02>
<fA03 i2="1"><s0>Antimicrob. agents chemother.</s0>
</fA03>
<fA05><s2>56</s2>
</fA05>
<fA06><s2>9</s2>
</fA06>
<fA08 i1="01" i2="1" l="ENG"><s1>Severe Acute Respiratory Syndrome Coronavirus Replication Inhibitor That Interferes with the Nucleic Acid Unwinding of the Viral Helicase</s1>
</fA08>
<fA11 i1="01" i2="1"><s1>ADEDEJI (Adeyemi O.)</s1>
</fA11>
<fA11 i1="02" i2="1"><s1>SINGH (Kamalendra)</s1>
</fA11>
<fA11 i1="03" i2="1"><s1>CALCATERRA (Nicholas E.)</s1>
</fA11>
<fA11 i1="04" i2="1"><s1>DEDIEGO (Marta L.)</s1>
</fA11>
<fA11 i1="05" i2="1"><s1>ENJUANES (Luis)</s1>
</fA11>
<fA11 i1="06" i2="1"><s1>WEISS (Susan)</s1>
</fA11>
<fA11 i1="07" i2="1"><s1>SARAFIANOS (Stefan G.)</s1>
</fA11>
<fA14 i1="01"><s1>Christopher S. Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine</s1>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>7 aut.</sZ>
</fA14>
<fA14 i1="02"><s1>Department of Biochemistry, University of Missouri</s1>
<s2>Columbia, Missouri</s2>
<s3>USA</s3>
<sZ>3 aut.</sZ>
<sZ>7 aut.</sZ>
</fA14>
<fA14 i1="03"><s1>Centro Nacional de Biotecnología-CSIC Spanish Council for Scientific Research, Campus Universidad Autónoma</s1>
<s2>Madrid</s2>
<s3>ESP</s3>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
</fA14>
<fA14 i1="04"><s1>Department of Microbiology, University of Pennsylvania, School of Medicine</s1>
<s2>Philadelphia, Pennsylvania</s2>
<s3>USA</s3>
<sZ>6 aut.</sZ>
</fA14>
<fA20><s1>4718-4728</s1>
</fA20>
<fA21><s1>2012</s1>
</fA21>
<fA23 i1="01"><s0>ENG</s0>
</fA23>
<fA43 i1="01"><s1>INIST</s1>
<s2>13334</s2>
<s5>354000504464350210</s5>
</fA43>
<fA44><s0>0000</s0>
<s1>© 2012 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45><s0>73 ref.</s0>
</fA45>
<fA47 i1="01" i2="1"><s0>12-0363176</s0>
</fA47>
<fA60><s1>P</s1>
</fA60>
<fA61><s0>A</s0>
</fA61>
<fA64 i1="01" i2="1"><s0>Antimicrobial agents and chemotherapy</s0>
</fA64>
<fA66 i1="01"><s0>USA</s0>
</fA66>
<fC01 i1="01" l="ENG"><s0>Severe acute respiratory syndrome (SARS) is a highly contagious disease, caused by SARS coronavirus (SARS-CoV), for which there are no approved treatments. We report the discovery of a potent inhibitor of SARS-CoV that blocks replication by inhibiting the unwinding activity of the SARS-CoV helicase (nsp13). We used a Förster resonance energy transfer (FRET)-based helicase assay to screen the Maybridge Hitfinder chemical library. We identified and validated a compound (SSYA10-001) that specifically blocks the double-stranded RNA (dsRNA) and dsDNA unwinding activities of nsp13, with 50% inhibitory concentrations (IC<sub>50</sub>
s) of 5.70 and 5.30 μM, respectively. This compound also has inhibitory activity (50% effective concentration [EC<sub>50</sub>
] = 8.95 μM) in a SARS-CoV replicon assay, with low cytotoxicity (50% cytotoxic concentration [CC<sub>50</sub>
] = >250 μM), suggesting that the helicase plays a still unidentified critical role in the SARS-CoV life cycle. Enzyme kinetic studies on the mechanism of nsp13 inhibition revealed that SSYA10-001 acts as a noncompetitive inhibitor of nsp13 with respect to nucleic acid and ATP substrates. Moreover, SSYA10-001 does not affect ATP hydrolysis or nsp13 binding to the nucleic acid substrate. SSYA10-001 did not inhibit hepatitis C virus (HCV) helicase, other bacterial and viral RNA-dependent RNA polymerases, or reverse transcriptase. These results suggest that SSYA10-001 specifically blocks nsp13 through a novel mechanism and is less likely to interfere with the functions of cellular enzymes that process nucleic acids or ATP. Hence, it is possible that SSYA10-001 inhibits unwinding by nsp13 by affecting conformational changes during the course of the reaction or translocation on the nucleic acid. SSYA10-001 will be a valuable tool for studying the specific role of nsp13 in the SARS-CoV life cycle, which could be a model for other nidoviruses and also a candidate for further development as a SARS antiviral target.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>002B02S</s0>
</fC02>
<fC02 i1="02" i2="X"><s0>002B05C02C</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE"><s0>Syndrome respiratoire aigu sévère</s0>
<s2>NM</s2>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Severe acute respiratory syndrome</s0>
<s2>NM</s2>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA"><s0>Síndrome respiratorio agudo severo</s0>
<s2>NM</s2>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE"><s0>Coronavirus</s0>
<s2>NW</s2>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG"><s0>Coronavirus</s0>
<s2>NW</s2>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA"><s0>Coronavirus</s0>
<s2>NW</s2>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE"><s0>Réplication</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG"><s0>Replication</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Replicación</s0>
<s5>03</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Inhibiteur</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Inhibitor</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Inhibidor</s0>
<s5>04</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Acide nucléique</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Nucleic acid</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Acido nucleico</s0>
<s5>05</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Virose</s0>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Viral disease</s0>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Virosis</s0>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Infection</s0>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Infection</s0>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Infección</s0>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="06" i2="X" l="FRE"><s0>Pathologie de l'appareil respiratoire</s0>
<s5>37</s5>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Respiratory disease</s0>
<s5>37</s5>
</fC07>
<fC07 i1="06" i2="X" l="SPA"><s0>Aparato respiratorio patología</s0>
<s5>37</s5>
</fC07>
<fC07 i1="07" i2="X" l="FRE"><s0>Pathologie des poumons</s0>
<s5>38</s5>
</fC07>
<fC07 i1="07" i2="X" l="ENG"><s0>Lung disease</s0>
<s5>38</s5>
</fC07>
<fC07 i1="07" i2="X" l="SPA"><s0>Pulmón patología</s0>
<s5>38</s5>
</fC07>
<fN21><s1>282</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
<affiliations><list><country><li>Espagne</li>
<li>États-Unis</li>
</country>
<region><li>Communauté de Madrid</li>
<li>Missouri (État)</li>
<li>Pennsylvanie</li>
</region>
<settlement><li>Madrid</li>
</settlement>
</list>
<tree><country name="États-Unis"><noRegion><name sortKey="Adedeji, Adeyemi O" sort="Adedeji, Adeyemi O" uniqKey="Adedeji A" first="Adeyemi O." last="Adedeji">Adeyemi O. Adedeji</name>
</noRegion>
<name sortKey="Calcaterra, Nicholas E" sort="Calcaterra, Nicholas E" uniqKey="Calcaterra N" first="Nicholas E." last="Calcaterra">Nicholas E. Calcaterra</name>
<name sortKey="Calcaterra, Nicholas E" sort="Calcaterra, Nicholas E" uniqKey="Calcaterra N" first="Nicholas E." last="Calcaterra">Nicholas E. Calcaterra</name>
<name sortKey="Sarafianos, Stefan G" sort="Sarafianos, Stefan G" uniqKey="Sarafianos S" first="Stefan G." last="Sarafianos">Stefan G. Sarafianos</name>
<name sortKey="Sarafianos, Stefan G" sort="Sarafianos, Stefan G" uniqKey="Sarafianos S" first="Stefan G." last="Sarafianos">Stefan G. Sarafianos</name>
<name sortKey="Singh, Kamalendra" sort="Singh, Kamalendra" uniqKey="Singh K" first="Kamalendra" last="Singh">Kamalendra Singh</name>
<name sortKey="Weiss, Susan" sort="Weiss, Susan" uniqKey="Weiss S" first="Susan" last="Weiss">Susan Weiss</name>
</country>
<country name="Espagne"><region name="Communauté de Madrid"><name sortKey="Dediego, Marta L" sort="Dediego, Marta L" uniqKey="Dediego M" first="Marta L." last="Dediego">Marta L. Dediego</name>
</region>
<name sortKey="Enjuanes, Luis" sort="Enjuanes, Luis" uniqKey="Enjuanes L" first="Luis" last="Enjuanes">Luis Enjuanes</name>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/PascalFrancis/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000038 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PascalFrancis/Checkpoint/biblio.hfd -nk 000038 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= SrasV1 |flux= PascalFrancis |étape= Checkpoint |type= RBID |clé= Pascal:12-0363176 |texte= Severe Acute Respiratory Syndrome Coronavirus Replication Inhibitor That Interferes with the Nucleic Acid Unwinding of the Viral Helicase }}
This area was generated with Dilib version V0.6.33. |