SrasV1, Main, Exploration, bibRecord, 001F85

Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris

Identifieur interne : 001F85 ( Main/Exploration ); précédent : 001F84; suivant : 001F86

Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris

Auteurs : Thi Thanh Hanh Nguyen [Corée du Sud, États-Unis] ; Hye-Jin Woo [Corée du Sud, États-Unis] ; Hee-Kyoung Kang [Corée du Sud, États-Unis] ; VAN DAO NGUYEN [Viêt Nam] ; Young-Min Kim [Corée du Sud] ; Do-Won Kim [Corée du Sud] ; Sul-Ah Ahn [Corée du Sud] ; YONGMEI XIA [République populaire de Chine] ; Doman Kim [États-Unis]

Source :

Biotechnology letters [ 0141-5492 ] ; 2012.

RBID : Pascal:12-0198879

Descripteurs français

Pascal (Inist)
- Flavonoïde, Inhibition, Peptidases, Syndrome respiratoire aigu sévère, Coronavirus, Pichia pastoris.

English descriptors

KwdEn :
- Coronavirus, Flavonoid, Inhibition, Peptidases, Pichia pastoris, Severe acute respiratory syndrome.

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. Recombinant 3CL^pro was expressed in Pichia pastoris GS 115 as a 42 kDa protein that displayed a K_m of 15 ± 2 μM with Dabcyl-KTSAVLQSGFRKME-Edans as substrate. Purified 3CL^pro was used for inhibition and kinetic assays with seven flavonoid compounds. The IC₅₀ of six flavonoid compounds were 47-381 μM. Quercetin, epigallocatechin gallate and gallocatechin gallate (GCG) displayed good inhibition toward 3CL^pro with IC₅₀ values of 73, 73 and 47 μM, respectively. GCG showed a competitive inhibition pattern with K_i value of 25 ± 1.7 μM. In molecular docking experiments, GCG displayed a binding energy of -14 kcal mol^-1 to the active site of 3CL^pro and the galloyl moiety at 3-OH position was required for 3CL^pro inhibition activity.

Affiliations:

Links toward previous steps (curation, corpus...)

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Le document en format XML

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<s2>214122 Jiangsu</s2>
<s3>CHN</s3>
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<country>République populaire de Chine</country>
<wicri:noRegion>214122 Jiangsu</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kim, Doman" sort="Kim, Doman" uniqKey="Kim D" first="Doman" last="Kim">Doman Kim</name>
<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Pediatrics, University of California</s1>
<s2>San Diego, CA 92103</s2>
<s3>USA</s3>
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<series><title level="j" type="main">Biotechnology letters</title>
<title level="j" type="abbreviated">Biotechnol. lett.</title>
<idno type="ISSN">0141-5492</idno>
<imprint><date when="2012">2012</date>
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</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Coronavirus</term>
<term>Flavonoid</term>
<term>Inhibition</term>
<term>Peptidases</term>
<term>Pichia pastoris</term>
<term>Severe acute respiratory syndrome</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Flavonoïde</term>
<term>Inhibition</term>
<term>Peptidases</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Coronavirus</term>
<term>Pichia pastoris</term>
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<front><div type="abstract" xml:lang="en">The 3C-like protease (3CL<sup>pro</sup>
) of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is vital for SARS-CoV replication and is a promising drug target. Recombinant 3CL<sup>pro</sup>
 was expressed in Pichia pastoris GS 115 as a 42 kDa protein that displayed a K<sub>m</sub>
 of 15 ± 2 μM with Dabcyl-KTSAVLQSGFRKME-Edans as substrate. Purified 3CL<sup>pro</sup>
 was used for inhibition and kinetic assays with seven flavonoid compounds. The IC<sub>50</sub>
 of six flavonoid compounds were 47-381 μM. Quercetin, epigallocatechin gallate and gallocatechin gallate (GCG) displayed good inhibition toward 3CL<sup>pro</sup>
 with IC<sub>50</sub>
 values of 73, 73 and 47 μM, respectively. GCG showed a competitive inhibition pattern with K<sub>i</sub>
 value of 25 ± 1.7 μM. In molecular docking experiments, GCG displayed a binding energy of -14 kcal mol<sup>-1</sup>
 to the active site of 3CL<sup>pro</sup>
 and the galloyl moiety at 3-OH position was required for 3CL<sup>pro</sup>
 inhibition activity.</div>
</front>
</TEI>
<affiliations><list><country><li>Corée du Sud</li>
<li>République populaire de Chine</li>
<li>Viêt Nam</li>
<li>États-Unis</li>
</country>
<region><li>Californie</li>
</region>
</list>
<tree><country name="Corée du Sud"><noRegion><name sortKey="Hanh Nguyen, Thi Thanh" sort="Hanh Nguyen, Thi Thanh" uniqKey="Hanh Nguyen T" first="Thi Thanh" last="Hanh Nguyen">Thi Thanh Hanh Nguyen</name>
</noRegion>
<name sortKey="Ahn, Sul Ah" sort="Ahn, Sul Ah" uniqKey="Ahn S" first="Sul-Ah" last="Ahn">Sul-Ah Ahn</name>
<name sortKey="Kang, Hee Kyoung" sort="Kang, Hee Kyoung" uniqKey="Kang H" first="Hee-Kyoung" last="Kang">Hee-Kyoung Kang</name>
<name sortKey="Kim, Do Won" sort="Kim, Do Won" uniqKey="Kim D" first="Do-Won" last="Kim">Do-Won Kim</name>
<name sortKey="Kim, Young Min" sort="Kim, Young Min" uniqKey="Kim Y" first="Young-Min" last="Kim">Young-Min Kim</name>
<name sortKey="Woo, Hye Jin" sort="Woo, Hye Jin" uniqKey="Woo H" first="Hye-Jin" last="Woo">Hye-Jin Woo</name>
</country>
<country name="États-Unis"><region name="Californie"><name sortKey="Hanh Nguyen, Thi Thanh" sort="Hanh Nguyen, Thi Thanh" uniqKey="Hanh Nguyen T" first="Thi Thanh" last="Hanh Nguyen">Thi Thanh Hanh Nguyen</name>
</region>
<name sortKey="Kang, Hee Kyoung" sort="Kang, Hee Kyoung" uniqKey="Kang H" first="Hee-Kyoung" last="Kang">Hee-Kyoung Kang</name>
<name sortKey="Kim, Doman" sort="Kim, Doman" uniqKey="Kim D" first="Doman" last="Kim">Doman Kim</name>
<name sortKey="Woo, Hye Jin" sort="Woo, Hye Jin" uniqKey="Woo H" first="Hye-Jin" last="Woo">Hye-Jin Woo</name>
</country>
<country name="Viêt Nam"><noRegion><name sortKey="Van Dao Nguyen" sort="Van Dao Nguyen" uniqKey="Van Dao Nguyen" last="Van Dao Nguyen">VAN DAO NGUYEN</name>
</noRegion>
</country>
<country name="République populaire de Chine"><noRegion><name sortKey="Yongmei Xia" sort="Yongmei Xia" uniqKey="Yongmei Xia" last="Yongmei Xia">YONGMEI XIA</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris

Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris

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Descripteurs français

English descriptors

Abstract

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