160 Perspecf'ives in Microbiology 



At inhibitory concentration, the compound has no effect 

 on the oxidative metabolism of the host tissue and only a 

 slight effect on cellular proliferation in tissue culture (38). 

 These findings may be taken as indications of some selec- 

 tivity in action. But the nature of the biosynthetic process 

 affected by the compound has not yet been identified, and 

 efforts to block the inhibitory effect with a variety of possi- 

 ble metabolites, including vitamin B12 or its corresponding 

 riboside moiety, as well as various purines and pyrimidines, 

 have been unsuccessful. 



A simpler compound, but not such a potent inhibitor of 

 influenza virus reproduction, is 2,5-dimethyl benzimidazole 

 (35, 36, 37). Like the chloro-substituted riboside, this sub- 

 stance inhibits the intracellular reproduction of influenza 

 viruses but has no effect on extracellular virus particles or 

 their adsorption. In contrast to the dichlororibofuranoside, 

 however, the inhibitory effect is not limited to an early 

 stage in the reproductive process. Although the degree of 

 inhibition is inversely related to the time of addition of 

 the compound, definite inhibition can be obtained during 

 the last part of the latent period (35). This substance also 

 fails to diminish tissue respiration at inhibitory concentra- 

 tion but does restrict cell growth in tissue culture (38). 

 Both the restriction in cell proliferation and the inhibition 

 of virus reproduction are reversible and disappear on re- 

 moval of the compound. Whether the inhibition of in- 

 fluenza virus reproduction produced by either of these 

 benzimidazole derivatives provides a positive advantage for 

 the functions of the infected cell remains to be demon- 

 strated. 



The results obtained thus far with inhibitory derivatives 

 of benzimidazole raise the possibility that a number of 

 processes that lead to the production of new virus particles 

 may be inhibited. The reduction in soluble antigenic ma- 

 terial (39), presumably chiefly protein, appears not to be 

 greatly different from the reduction in the yield of virus 



