Antiviral effects of a thiol protease inhibitor on foot-and-mouth disease virus.
The thiol protease inhibitor E-64 specifically blocks autocatalytic activity of the leader protease of foot-and-mouth disease virus (FMDV) and interferes with cleavage of the structural protein precursor in an in vitro translation assay programmed with virion RNA. Experiments with FMDV-infected cells and E-64 or a membrane-permeable analog, E-64d, have confirmed these results and demonstrated interference in virus assembly, causing a reduction in virus yield. In addition, there is a lag in the appearance of virus-induced cellular morphologic alterations, a delay in cleavage of host cell protein p220 and in shutoff of host protein synthesis, and a decrease in viral protein and RNA synthesis. The implications of using E-64-based compounds as potential antiviral agents for FMDV are discussed.
Kleina
L G
LG
Plum Island Animal Disease Center, U.S. Department of Agriculture, Greenport, New York 11944-0848.
Grubman
M J
MJ
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D005537:Aphthovirus / Q000187:drug effects* / Q000502:physiology; D002417:Cattle; D002460:Cell Line; D007668:Kidney; D007700:Kinetics; D011480:Protease Inhibitors / Q000494:pharmacology*; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D015678:Viral Structural Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D011480:Protease Inhibitors; D011498:Protein Precursors; D015678:Viral Structural Proteins