Inhibition of adenovirus infection with protease inhibitors

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 IC50 of 30, 40 and 80 nM with N-ethylmaleimide, leupeptin and E64c, respectively. Several lines of evidence suggest that inhibition of infectious virus formation operated through the inhibition of the viral protease rather than cellular toxicity: (a) the yield of physical particles declined only 4-5-fold, while that of infectious virus declined 3-7 orders of magnitude, (b) these particles contained unprocessed precursor proteins and (c) pulse-chase experiments showed that the inhibitors prevented the efficient processing of viral precursor proteins. We conclude that the cysteine protease inhibitors efficiently depress the formation of infectious adenovirus by inhibiting the viral protease.