220 F. L. HORSFALL, JR. 



In marked contrast to the large amount of information that has been 

 assembled relative to inhibition of virus multiplication, very little is known 

 regarding modification of the host cell damage that is so commonly associated 

 with multiplication. There is as yet no evidence that any inhibitor of a bio- 

 synthetic process will protect the virus-infected cell from the cytopathogenic 

 effects of the agent (Tamm, 1958). 



As indicated in an earlier section, ^-fluorophenylalanine, although markedly 

 inhibitory against the multiplication of poliovirus virus, had no modifying 

 effect on the cytopathogenicity of the agent in HeLa cells (Ackermann et al., 

 1954). Although a culture filtrate of Penicillium stoloniferum, designated 

 M-8450, prevented the cytopathogenic effects of all three types of polio- 

 virus on monkey testicular cells in vitro (Hull and Lavelle, 1953), the 

 mechanism responsible for the modification remains unclear. It is not yet 

 known whether the filtrate prevents infection, inhibits virus multiplication, 

 or acts in some other manner. 



A product from Achromobacter xerosis, designated Xerosin, has been shown 

 to modify some secondary virus-induced lesions in the mouse lung but does not 

 inhibit virus multiplication (Groupe and Dougherty, 1956; Ginsberg, 1955). 

 There is no evidence that the substance decreases damage to the virus- 

 infected cell per se. 



VII. Current Status of Inhibition of Multiplication 



Within the last few years many striking advances have been recorded 

 regarding inhibition of multiplication of animal viruses. Many compounds of 

 diverse nature have been discovered to possess inhibitory activity in greater 

 or lesser degree. Procedures have been devised for precise measurement of 

 inhibitory potency. A technique has been developed which permits the 

 selection of favorable alterations in chemical structure. Through its 

 use compounds of greatly enhanced inhibitory potency have been 

 produced. 



Some inhibitory compounds of known structure have been shown to 

 interfere with biosynthetic processes involving large molecular substances, 

 i.e., nucleic acids and proteins, in the host cell. In a few instances, it has been 

 possible to correlate the inhibitory activity with the interfering effect on host 

 cell biosynthetic systems. However, it has not yet been feasible to demon- 

 strate that the synthesis of a virus precursor material per se is affected by any 

 inhibitory compound. 



All potent inhibitory compounds have been found to have some effect on 

 host cell metabolism, whenever such an effect has been sought (Tamm, 1958). 

 Because of the lack of knowledge of any specific chemical features of animal 

 virus components, approaches to the inhibition of biosynthetic systems have 



