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Green tea catechins have been reported to inhibit proteases involved in cancer metastasis and infection by influenza virus and HIV. To date there are no effective anti-adenoviral therapies. Consequently, we studied the effect of green tea catechins, and particularly the predominant component, epigallocatechin-3-gallate (EGCG), on adenovirus infection and the viral protease adenain, in cell culture...
Adenoviruses encode a cysteine protease, adenain, required for uncoating and virion maturation. Adenain activity is regulated by an 11-amino-acid peptide cofactor thiol-bonded distal to the active site. Structural and experimental data suggest that the peptide might stabilize adenain in an optimal conformation for enzyme activity by bridging two noncontiguous regions of the molecule. The sequence...
The catalytic activity of the adenovirus cysteine peptidase is increased by a specific 11-amino-acid peptide adduct (GVQSLKRRRCF, referred to as pVIc). To identify additional peptides which might bind and alter the activity of the protease, a cysteine-constrained random peptide phage library was screened. Of 29 different phages which were isolated, 7 contained the consensus sequence VEGGS. Despite...
The effect of a series of cysteine and serine protease inhibitors was tested on the growth of human adenovirus type 2 in tissue culture. In accordance with the nature of the adenovirus protease, only the cysteine protease inhibitors were effective in significantly reducing the production of infectious virus. Addition of the inhibitors to the medium 18 h after infection gave IC 50 of...
Infection with the adenovirus type 2 ts1 mutant at the nonpermissive temperature resulted in the production of noninfectious virions. This has been ascribed to the P137L mutation in the virus-encoded cysteine protease which causes a defect in protease activity. Here we have examined the ts1 defect in detail as a means of learning more about the viral protease. The ts1 protease accumulated in the nucleus...
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