INHIBITION OF MULTIPLICATION 211 



DAB interferes with the synthesis of RNA in monkey kidney cells in vitro 

 but, unlike DRB, it also markedly interferes with the synthesis of protein 

 (Nemes and Tamm, 1958). These findings may be correlated with the longer 

 interval during which the inhibitory activity of DAB is manifest. 



The compound shows relatively low activity, on a molar basis, as an 

 inhibitor of influenza virus multiplication (Tamm, 1956b) and is only slightly 

 more potent as an inhibitor of poliovirus reproduction (Tamm and Nemes, 

 1957). 



B. Resume' of Inhibition during Latent Period 

 As shown hi Table I, the 7 substances that have been demonstrated to 

 inhibit multiplication durmg the latent period have very little in common; 

 3 are derivatives of benzimidazole. one is an analog of methionine, one is a 

 bacterial capsular polysaccharide, one is a derivative of phenyl caproic acid, 

 and one is an analog of phenylalanine. Only one, K. pneumoniae, type B, 

 capsular polysaccharide (Fr. B), has been shown to inhibit reproduction 

 during the latent period in an intact mammalian host, the mouse. Five show 

 such inhibitory activity either in host tissue, i.e., chorioallantoic membrane, 

 or in host cells, i.e., monkey kidney or HeLa cells, in vitro; one, in the 

 de-embryonated egg. 



Only five viruses, i.e., pneumonia virus of mice (PVM), influenza A (IAV), 

 influenza B (IBV), poliovirus, type 2 (Polio, 2), and poliovirus, type 3 

 (Polio, 3) have been shown to be inhibited during the latent period. Only one 

 compound, i.e., a chloro-ribofuranosyl derivative of benzimidazole (DRB), 

 inhibits two of these viruses during the latent period. Four compounds, i.e., 

 2, 5-dimethylbenzimidazole (MB), methoxinine, caprochlorone and a chloro- 

 arabinopyranosyl derivative of benzimidazole (DAB), are inhibitory through- 

 out the latent period; all but methoxinine are somewhat inhibitory for some 

 time after this interval. Only 3 substances show inhibitory activity that is 

 restricted to the early part of the latent period, i.e, K. pneumoniae, Type B, 

 capsular polysaccharide (Fr. B), DRB, and FPA. 



There are indications of the biochemical mechanism of inhibitory activity 

 for only four compounds: (1) Methoxinine blocks some function of methionine 

 metabolism; (2) DRB interferes with the synthesis of RNA; (3) FPA interferes 

 with phenylalanine metabolism; (4) DAB interferes with the synthesis of both 

 RNA and protein. If virus precursor RNA is synthesized early in the latent 

 period of influenza and polioviruses, it might be expected that DRB would 

 inhibit reproduction exclusively during the early part of the interval, as is 

 the case in both instances. 



C. Inhibition after Latent Period 

 The only substances that appear to have some inhibitory effect on multi- 

 plication after the latent period has been completed are certain of those which 



