Mark Denison
Last active: 2/22/2016

Coronavirus protein processing and RNA synthesis is inhibited by the cysteine proteinase inhibitor E64d.

Kim JC, Spence RA, Currier PF, Lu X, Denison MR
Virology. 1995 208 (1): 1-8

PMID: 11831690 · DOI:10.1006/viro.1995.1123

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.

MeSH Terms (10)

Animals Cells, Cultured Cysteine Proteinase Inhibitors Leucine Mice Murine hepatitis virus Protein Processing, Post-Translational RNA, Viral Viral Proteins Virus Replication

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