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 cystei ne protease inhibitors were effective in significantly reducing the pr oduction of infectious virus. Addition of the inhibitors to the medium 18 h after infection gave IC50 of 30, 40 and 80 nM with N-ethylmaleim ide, leupeptin and E64c, respectively. Several lines of evidence sugge st that inhibition of infectious virus formation operated through the inhibition of the viral protease rather than cellular toxicity: (a) th e yield of physical particles declined only 4-5-fold, while that of in fectious virus declined 3-7 orders of magnitude, (b) these particles c ontained unprocessed precursor proteins and (c) pulse-chase experiment s showed that the inhibitors prevented the efficient processing of vir al precursor proteins. We conclude that the cysteine protease inhibito rs efficiently depress the formation of infectious adenovirus by inhib iting the viral protease.