Coronavirus main proteinase (3CLpro) structure: Basis for design of anti-SARS drugs
Identifieur interne : 006411 ( Main/Exploration ); précédent : 006410; suivant : 006412Coronavirus main proteinase (3CLpro) structure: Basis for design of anti-SARS drugs
Auteurs : Kanchan Anand [Allemagne] ; John Ziebuhr [Allemagne] ; Parvesh Wadhwani [Allemagne] ; Jeroen R. Mesters [Allemagne] ; Rolf Hilgenfeld [Allemagne]Source :
- Science : (Washington, D.C.) [ 0036-8075 ] ; 2003.
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Abstract
A novel coronavirus has been identified as the causative agent of severe acute respiratory syndrome (SARS). The viral main proteinase (MPro, also called 3CLPro), which controls the activities of the coronavirus replication complex, is an attractive target for therapy. We determined crystal structures for human coronavirus (strain 229E) MPro and for an inhibitor complex of porcine coronavirus [transmissible gastroenteritis virus (TGEV)] MPro, and we constructed a homology model for SARS coronavirus (SARS-CoV) MPro. The structures reveal a remarkable degree of conservation of the substrate-binding sites, which is further supported by recombinant SARS-CoV MPro-mediated cleavage of a TGEV MPro substrate. Molecular modeling suggests that available rhinovirus 3CPro inhibitors may be modified to make them useful for treating SARS.
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Mesters</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institute of Biochemistry, University of Lübeck</s1><s2>23538 Lübeck</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>23538 Lübeck</wicri:noRegion><wicri:noRegion>University of Lübeck</wicri:noRegion><wicri:noRegion>23538 Lübeck</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Institute of Molecular Biotechnology</s1><s2>07745 Jena</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>07745 Jena</wicri:noRegion><wicri:noRegion>Institute of Molecular Biotechnology</wicri:noRegion><wicri:noRegion>Institute of Molecular Biotechnology</wicri:noRegion></affiliation></author><author><name sortKey="Hilgenfeld, Rolf" sort="Hilgenfeld, Rolf" uniqKey="Hilgenfeld R" first="Rolf" last="Hilgenfeld">Rolf Hilgenfeld</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institute of Biochemistry, University of Lübeck</s1><s2>23538 Lübeck</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>23538 Lübeck</wicri:noRegion><wicri:noRegion>University of Lübeck</wicri:noRegion><wicri:noRegion>23538 Lübeck</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Institute of Molecular Biotechnology</s1><s2>07745 Jena</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>07745 Jena</wicri:noRegion><wicri:noRegion>Institute of Molecular Biotechnology</wicri:noRegion><wicri:noRegion>Institute of Molecular Biotechnology</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Science : (Washington, D.C.)</title><title level="j" type="abbreviated">Science : (Wash. D.C.)</title><idno type="ISSN">0036-8075</idno><imprint><date when="2003">2003</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Science : (Washington, D.C.)</title><title level="j" type="abbreviated">Science : (Wash. D.C.)</title><idno type="ISSN">0036-8075</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Genetics</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Génétique</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A novel coronavirus has been identified as the causative agent of severe acute respiratory syndrome (SARS). The viral main proteinase (M<sup>Pro</sup>, also called 3CL<sup>Pro</sup>), which controls the activities of the coronavirus replication complex, is an attractive target for therapy. We determined crystal structures for human coronavirus (strain 229E) M<sup>Pro</sup> and for an inhibitor complex of porcine coronavirus [transmissible gastroenteritis virus (TGEV)] M<sup>Pro</sup>, and we constructed a homology model for SARS coronavirus (SARS-CoV) M<sup>Pro</sup>. The structures reveal a remarkable degree of conservation of the substrate-binding sites, which is further supported by recombinant SARS-CoV M<sup>Pro</sup>-mediated cleavage of a TGEV M<sup>Pro</sup> substrate. Molecular modeling suggests that available rhinovirus 3C<sup>Pro</sup> inhibitors may be modified to make them useful for treating SARS.</div></front></TEI><affiliations><list><country><li>Allemagne</li></country><region><li>Bavière</li><li>District de Basse-Franconie</li></region><settlement><li>Wurtzbourg</li></settlement></list><tree><country name="Allemagne"><noRegion><name sortKey="Anand, Kanchan" sort="Anand, Kanchan" uniqKey="Anand K" first="Kanchan" last="Anand">Kanchan Anand</name></noRegion><name sortKey="Anand, Kanchan" sort="Anand, Kanchan" uniqKey="Anand K" first="Kanchan" last="Anand">Kanchan Anand</name><name sortKey="Hilgenfeld, Rolf" sort="Hilgenfeld, Rolf" uniqKey="Hilgenfeld R" first="Rolf" last="Hilgenfeld">Rolf Hilgenfeld</name><name sortKey="Hilgenfeld, Rolf" sort="Hilgenfeld, Rolf" uniqKey="Hilgenfeld R" first="Rolf" last="Hilgenfeld">Rolf Hilgenfeld</name><name sortKey="Mesters, Jeroen R" sort="Mesters, Jeroen R" uniqKey="Mesters J" first="Jeroen R." last="Mesters">Jeroen R. Mesters</name><name sortKey="Mesters, Jeroen R" sort="Mesters, Jeroen R" uniqKey="Mesters J" first="Jeroen R." last="Mesters">Jeroen R. Mesters</name><name sortKey="Wadhwani, Parvesh" sort="Wadhwani, Parvesh" uniqKey="Wadhwani P" first="Parvesh" last="Wadhwani">Parvesh Wadhwani</name><name sortKey="Ziebuhr, John" sort="Ziebuhr, John" uniqKey="Ziebuhr J" first="John" last="Ziebuhr">John Ziebuhr</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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