Publication Date:
2003-05-15
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anand, Kanchan -- Ziebuhr, John -- Wadhwani, Parvesh -- Mesters, Jeroen R -- Hilgenfeld, Rolf -- New York, N.Y. -- Science. 2003 Jun 13;300(5626):1763-7. Epub 2003 May 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Biochemistry, University of Lubeck, D-23538 Lubeck, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12746549" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Chloromethyl Ketones/chemistry/metabolism
;
Amino Acid Sequence
;
*Antiviral Agents
;
Binding Sites
;
Catalytic Domain
;
Coronavirus 229E, Human/*enzymology
;
Crystallization
;
Crystallography, X-Ray
;
Cysteine Endopeptidases/*chemistry/metabolism
;
Cysteine Proteinase Inhibitors/chemistry/metabolism
;
Dimerization
;
*Drug Design
;
Humans
;
Isoxazoles/chemistry/metabolism/pharmacology
;
Models, Molecular
;
Molecular Sequence Data
;
Protein Conformation
;
Protein Structure, Secondary
;
Protein Structure, Tertiary
;
Pyrrolidinones/chemistry/metabolism/pharmacology
;
Recombinant Proteins/chemistry/metabolism
;
SARS Virus/*drug effects/*enzymology
;
Sequence Alignment
;
Sequence Homology, Amino Acid
;
Severe Acute Respiratory Syndrome/drug therapy
;
Transmissible gastroenteritis virus/enzymology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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