214 F. L. HORSFALL, JR. 



Dulbecco and Vogt, 1954; Ackermann and Maassab, 1954a) and do not 

 emerge suddenly, as at the burst of phage-producing bacteria. The mechanism 

 of release is not fully understood but it seems clear that certain viruses 

 escape from infected cells which remain morphologically intact. This occurs 

 most obviously with influenza virus in tissues of the chick embryo, the 

 system in which release has been most extensively studied (Henle, 1949; 

 Fazekas de St. Groth and Cairns, 1952; Murphy and Bang, 1952; Morgan et ah, 

 1956). 



The only compound that has been implicated in the inhibition of release is 

 a-amino-^-methoxyphenylmethanesulfonic acid (Ackermann and Maassab, 

 1954a,b). This compound interferes with the release of newly formed 

 influenza A virus particles from the chorioallantoic membrane in vitro. This 

 effect is prevented by the receptor-destroying enzyme obtained from V. 

 cJiolerae extracts. It has been proposed (Ackermann and Maassab, 1954b) 

 that one function of the influenza virus enzyme is to facilitate the release of 

 virus particles from the infected host cell. As indicated in an earlier section, 

 the compound does not inhibit the multiplication of influenza virus during the 

 latent period but does interfere with the initiation of infection (Ackermann 

 and Maassab, 1954b). 



The great bulk of substances rer>orted to have an inhibitory effect on animal 

 virus multiplication have not been studied in single-cycle multiplication 

 experiments. Because of the lack of precise kinetic data, it is not feasible 

 to assign their inhibitory activity to any stage or step in the process of 

 reproduction. At present, therefore, they must be grouped together in an 

 unsatisfactory category: substances that are inhibitory at undetermined 

 stages of the multiplication cycle. 



V. Chemical Structure and Inhibitory Activity 



In recent reviews (Matthews and Smith, 1955; Hurst and Hull, 1956; 

 Horsfall and Tamm, 1957; Tamm, 1958), almost all known inhibitory 

 substances have been discussed in some detail. At the risk of some repetition, 

 it seems desirable to consider the activity of certain arbitrarily selected groups 

 of compounds of known structure for which there are some indications of the 

 mechanism of their inhibitory effects. 



A. Benzimidazoles and Derivatives 



More is known of the chemical structure-inhibitory activity relationships 

 with derivatives of benzimidazoles than with any other group of chemical 

 compounds (Tamm, 1958). Beginning in 1952, Tamm and his co-workers 

 undertook a systematic evaluation of the effects of a variety of substitutions 

 in the benzimidazole molecule and measured inhibitory activity with a 



