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

Abstract:

: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.

journal_name

Virology

journal_title

Virology

authors

Kim JC,Spence RA,Currier PF,Lu X,Denison MR

doi

10.1006/viro.1995.1123

subject

Has Abstract

pub_date

1995-04-01 00:00:00

pages

1-8

issue

1

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(85)71123-3

journal_volume

208

pub_type

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