PMID: 11900346Mar 20, 2002Paper

Peptidyl diazomethyl ketones inhibit the human rhinovirus 3C protease: effect on virus yield by partial block of P3 polyprotein processing

Antiviral Chemistry & Chemotherapy
M A MurrayL M Babe

Abstract

The efficacy of a series of diazomethyl ketones (DMKs) was measured in rhinovirus-infected cultures and against the HRV14 3C protease. Their specificity and potency were confirmed against purified recombinant enzyme expressed in a yeast secretion system. An internally quenched fluorescent peptide substrate was used to assess the potency against the enzyme, obtaining a 50% inhibitory concentration (IC50) of 1 microM for both Z-L-F-Q-CHN2 and Z-V-L-F-Q-CHN2, while a lower affinity was observed for Z-F-Q-CHN2. The tripeptide Z-L-F-Q-CHN2 blocked viral replication with an IC50 value of 30 microM as judged by the reduction in viral induced cytopathy of HeLa-H1 cells, as well as a marked reduction in viral plaque formation (50% effective concentration=20 microM). Western blot analysis of viral proteins from infected cells indicates that this inhibitor works specifically by blocking viral polyprotein maturation, displaying a reduction of detectable 3C protease and an accumulation of the 3CD polypeptide. These results indicate that DMK inhibitors of the 3C protease have antiviral potency. Furthermore, the pattern of viral protein processing observed suggests that reducing the concentration of mature HRV 3C protease even in the presence...Continue Reading

References

Jan 1, 1990·Annual Review of Microbiology·A C Palmenberg
Oct 25, 1984·Nucleic Acids Research·G StanwayJ W Almond
Dec 20, 1996·Journal of Medicinal Chemistry·S E WebberS L Binford
Nov 5, 1997·Archives of Biochemistry and Biophysics·G J DavisE C Villarreal
Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·A R KhanM N James
Oct 3, 1999·Antimicrobial Agents and Chemotherapy·A K PatickS T Worland

❮ Previous
Next ❯

Citations

Apr 3, 2008·Medicinal Research Reviews·Armando M De PalmaJohan Neyts

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Acute viral rhinopharyngitis

Acute viral rhinopharyngitis, also known as "common cold", is an acute, self-limiting viral infection of the upper respiratory tract involving the nose, sinuses, pharynx and larynx. Discover the latest research on acute viral rhinopharyngitis here.