Chemical Inhibition of Viruses 159 



moniae, are active as inhibitors of some small viruses, for 

 example, pneumonia virus of mice (30), though not for 

 other viruses in the same host species. Compounds of low 

 molecular weight and precisely known structure, like cer- 

 tain chloro-substituted N-glycosides of benzimidazoles, are 

 potent inhibitors of influenza virus reproduction in a tissue 

 culture system and also are active in the chick embryo and 

 in the mouse (38). Numerous other compounds, including 

 analogues of amino acids (2, 6), purine analogues (19), and 

 certain inhibitors of cell metabolic systems (1,4, 32), have 

 been reported to have inhibitory activity (15). Only certain 

 substances that appear to cause inhibition of the intracellu- 

 lar process of virus reproduction are considered in this 

 communication. Compounds that inactivate extracellular 

 virus particles, prevent their adsorption to susceptible cells, 

 or affect the responses of tissues without affecting reproduc- 

 tion are outside the scope of this discussion. 



The 5,6-dichloro derivate of benzimidazole ribofurano- 

 side provides an interesting example of inhibitory activity 

 with an animal virus (38). This compound, which is related 

 in structure both to a moiety of vitamin B12 and to adeno- 

 sine, inhibits an early stage in the intracellular reproduc- 

 tion of influenza viruses. It has no effect upon extracellular 

 virus particles and does not diminish adsorption of the 

 virus by host cells. When the substance is added after pene- 

 tration of the host cells has occurred, the yield of new virus 

 particles is diminished. The extent of the inhibition is in- 

 versely related to the time elapsed before the compound is 

 added. Each of the biologically measurable components 

 that result from the multiplication of influenza virus ap- 

 pears in decreased concentration. Infective virus particles, 

 hemagglutinating particles, and even soluble complement- 

 fixing antigen develop in diminished amount (39). There 

 is as yet no decisive evidence that any material with virus 

 specificity increases more than another in the presence of 

 this compound. 



