PubMed Journals: Science
Source: PMID: 12746549
⇦ ⇨ Science. 2003 Jun 13;300(5626):1763-7. Epub
⇩ 2003 May 13.
Coronavirus main proteinase (3CLpro) structure:
basis for design of anti-SARS drugs.
Anand K(1), Ziebuhr J, Wadhwani P, Mesters
JR, Hilgenfeld R.
(1) Institute of Biochemistry, University
of Lübeck, D-23538 Lübeck, Germany.
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.
DOI: 10.1126/science.1085658 PMID: 12746549
[Indexed for MEDLINE]