218 F. L. HORSFALL, JR. 



^-Fluorophenylalanine inhibits the multiplication of GD VII virus 

 (Pearson et al., 1952) and poliovirus, type 3, in HeLa cell in vitro (Ackermann 

 et al., 1954). In the latter instance, the inhibition was completely reversed by 

 phenylalanine. ^-Fluorophenylalanine may be regarded as an inhibitor of 

 protein synthesis (Halvorson and Spiegelman, 1952). The compound inhibited 

 the multiplication of HeLa cells at virus inhibitory concentration. Although 

 it completely inhibited poliovirus virus multiplication, it did not prevent 

 the cytopathogenic effect of the virus and the distintegration of infected cells 

 proceeded at the usual rate. 



The results obtained with amino acid analogs are compatible with the view 

 that these compounds interfere with or alter protein synthesis. In most 

 instances, the inhibition of virus multiplication produced by the analog is 

 prevented or reversed by the appropriate natural amino acid. 



C. Purine and Pyrimidine Analogs 



Relatively few analogs of purine or pyrimidine bases have been found to 

 act as effective inhibitors of animal virus multiplication (Matthews and Smith, 

 1955). 



Certain halogenated purines inhibit the multiplication of vaccinia virus in 

 tissue culture (Thompson et al., 1950) but the inhibitory effect is not prevented 

 by natural purines. 



2, 6-Diaminopurine inhibits the multiplication of vaccinia virus in tissue 

 culture (Thompson et al., 1950), Russian spring-summer encephalitis virus in 

 tissue culture (Friend, 1951), and poliovirus, type 2, in tissue culture (Brown, 

 1952). In all instances, the inhibition was partially reversed by adenine. The 

 multiplication of a number of other animal viruses was unaffected by this 

 purine analog. 



5-Chlorouridine or 5-hydroxyuridine inhibit the multiplication of GD VII 

 virus in mouse brain tissue culture (Rafelson et al., 1951; Pearson et al., 1956). 

 In both instances uridine partially reverses the inhibition. Various other 

 pyrimidine analogs have not shown inhibitory effects with a variety of animal 

 viruses. 



On the basis of extensive studies with plant and bacterial viruses (Matthews 

 and Smith, 1955), it has been suggested that purine and pyrimidine analogs 

 show inhibitory activity, because on incorporation into nucleic acids they 

 render them biologically nonfunctional. 



D. Compounds Affecting Oxidative Metabolism 



Marked alterations in the energy-yielding metabolism of host cells regularly 

 lead to reduction in their capacity to support virus multiplication. Because 

 the process of reproduction of viruses appears to be intimately linked to the 



