INHIBITION OF MULTIPLICATION 221 



been developed at the level of reactions which probably are common to both 

 virus and host cell. As Tamm (1958) has emphasized, there is now impressive 

 evidence that the synthesis of virus materials in host cells takes place in the 

 absence of a limiting virus membrane. This and the intimate dependence of 

 virus synthesis on host cell metabolism raise an important question: Will it be 

 possible to inhibit the production of virus precursor materials in the virus- 

 infected cell without also interfering with the synthesis of essential host 

 materials? Although the question cannot be answered decisively on present 

 evidence, it seems possible that quantitative differences in biosynthetic 

 conditions, rates, and requirements may permit the process of multiplication 

 to be selectively inhibited. Some inhibitory compounds have, in fact, already 

 shown a moderate degree of selectivity and give evidence of possessing 

 encouraging quantitative differences in inhibitory activity and host cell 

 toxicity. 



Relatively few animal viruses have been studied intensively in inhibition 

 experiments. Pneumonia virus of mice, vaccinia virus, influenza virus, and 

 polioviruses have for various reasons been selected as model agents in most 

 studies. All investigations bearing on inhibition during the latent period have 

 been performed with one or another of these viruses. Even within this small 

 group of viruses, inhibitory compounds have shown strikingly different 

 effects. In numerous instances, compounds that are highly potent against 

 the multiplication of one virus are considerably less active or are inactive 

 against that of another. In only an occasional instance has it been feasible to 

 suggest a basis for such differences in inhibitory activity. 



The great majority of inhibitory compounds have been shown to be active 

 in host cell systems in vitro. Only a small number of compounds so far have 

 been demonstrated to inhibit virus multiplication in the intact animal host. 

 Many inhibitory compounds possess such low activity on a weight basis that 

 it has not been feasible to use them at the desired concentration in the intact 

 host. Among the more potent compounds which show relatively high activity, 

 only a few have manifested selectivity of a degree sufficient to permit their 

 use in amounts that were not toxic for the animal host. 



With very few exceptions, compounds that are potent inhibitors of virus 

 multiplication have given disappointing results in chemotherapeutic 

 experiments. Only in a single instance, i.e., pneumonia virus of mice, has it 

 been possible with an inhibitory substance to modify an experimental virus 

 disease in favor of the host after gross lesions have appeared. As was stated 

 earlier, no inhibitory material has as yet been shown to be useful in the 

 management of any naturally occurring virus disease of animals or man. 

 Whether inhibitory compounds will be brought to a stage of development in 

 which they will have useful applications is an unanswerable and probably not 

 a very important question. Their quest has already opened large new vistas 



