Inhibition of Influenza Virus Multiplication by Alkyl Derivatives of Benzimidazole I. Kinetic Aspects of Inhibition by 2,5-dimethylbenzimidazole as Measured by Infectmty Titrations

That 2,5-dimethylbenzimidazole inhibits the multiplication of influenza A or B virus in chorioallantoic membrane cultures in vitro was reported in an earlier paper (1). The evidence obtained indicated that the compound exerted an inhibitory effect when added after the host tissue had been infected by the virus. Moreover, the inhibitory effect was reversible: after a period during which multiplication was suppressed, reduction in the concentration of the substance resulted in undiminished multiplication of the virus in treated membranes. In addition, the finding that the compound had, at inhibitory levels, no effect on the oxygen consumption of membranes suggested that metabolic pathways other than those concerned with oxidative reactions were affected. One approach to an understanding of the mechanism of the inhibitory action of 2,5-dimethylbenzimidazole is to obtain answers to the following questions: (a) How does the compound affect the curve of increase in concentration of the virus? (b) What phases of the multiplication cycle of the virus are affected by the compound? The concept that multiplication of influenza virus takes place in discrete cycles, each of which can be subdivided into (a) an adsorptive period, (b) a plateau or latent period, and (c) an incremental period, is supported by considerable experimental evidence (2-7). The results reported in this paper are in accord with this conception. In this communication, experimental results are presented which provide a basis for an analysis of the kinetics of inhibition of influenza B virus multiplication by 2,5-dimethylbenzimidazole. Infectivity titrations were used throughout this study so that events occurring in the first cycle of multiplication could be examined. In the accompanying papers (8, 9), results obtained by hemagglutination titrations are presented and the inhibitory effects of a number of alkyl derivatives of benzimidazole are described.