Document Detail


Coronavirus protein processing and RNA synthesis is inhibited by the cysteine proteinase inhibitor E64d.
MedLine Citation:
PMID:  11831690     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mouse hepatitis virus strain A59 (MHV-A59) encodes within the 22-kb gene 1 a large polyprotein containing three proteinase domains with proven or predicted cysteine catalytic residues. E64d, a specific, irreversible inhibitor of cysteine (thiol) proteinases, inhibits the processing of the gene 1 polyprotein. Specifically, E64d blocks the carboxy-terminal cleavage of p65. E64d also inhibits replication of MHV-A59 in murine DBT cells in a dose-dependent manner, resulting in reduced virus titers and viral syncytia formation. This inhibition of replication is associated with a rapid shutoff of new viral RNA synthesis, in a manner similar to that seen in the presence of cycloheximide. The E64d-associated inhibition of RNA synthesis likely results from E64d-specific inhibition of processing of the gene 1 polyprotein, resulting in inactive proteinase or replicase proteins. These results indicate that processing of the MHV-A59 gene 1-encoded polyprotein is required throughout infection to sustain RNA synthesis and virus replication.
Authors:
J C Kim; R A Spence; P F Currier; X Lu; M R Denison
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Virology     Volume:  208     ISSN:  0042-6822     ISO Abbreviation:  Virology     Publication Date:  1995 Apr 
Date Detail:
Created Date:  2002-02-07     Completed Date:  2002-02-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0110674     Medline TA:  Virology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1-8     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Vanderbilt Medical School, Nashville, Tennessee 37232-2581, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cells, Cultured
Cysteine Proteinase Inhibitors / pharmacology*
Leucine / analogs & derivatives*,  pharmacology*
Mice
Murine hepatitis virus / drug effects*,  physiology*
Protein Processing, Post-Translational / drug effects
RNA, Viral / biosynthesis,  drug effects
Viral Proteins / genetics,  metabolism*
Virus Replication / drug effects
Grant Support
ID/Acronym/Agency:
R01 AI-26603/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Cysteine Proteinase Inhibitors; 0/RNA, Viral; 0/Viral Proteins; 0/gene 1 protein, Coronavirus; 61-90-5/Leucine; 88321-09-9/aloxistatin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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