Original Articles
The Effect of N1, N1-Anhydrobis-(β-Hydroxyethyl) Biguanide Hydrochloride Against the Growth of Sendai Virus in HeLa Cell Cultures
1962 年 15 巻 4 号 p. 168-173
詳細
1962 年 15 巻 4 号 p. 168-173
In 1960, Melander1) reported that, among various types of synthetic biguanides tested for anti-influenza activity, N1, N1-anhydrobis-(£>-hydroxyethyl) biguanide HCl (ABOB) was active against influenza A (PR8) and B (Lee) viruses in mice. In his experiment, suppression of lung consolidation was used as the criterion of effectiveness. However, the effect of reducing lung pathology with this compound should be said rather marginal.
Similar experiment was performed in our laboratory against PR8 virus infection in the mice of dd strain2) under the established infection condition3l, but delay in the death of mice receiving ABOB was hardly observed. Scoring the lung consolidation, again no significant effect was observed. Meanwhile, clinical application of the compound has been reported4)5), and the fact that the toxicity af ABOB is extremely low seemed to suggest the importance of exploring the compound both in laboratory and clinic.
Although the significance of the biguanide structure of ABOB for its antiviral activity is unclear, it should be emphasized that three antibiotics having guanidine or amidine groups in their structure are known to have antiviral activity; noformicin6,7) and myxoviromycin8,9,10) are active against influenza in mice, and netropsin11) (sinanomycin 12) against vaccinia in mice. The synthetic guanidines described by Lum et al.13) also revealed antiviral activity against influenza virus infection in mice.
Having these considerations in mind, possible antiviral effect of ABOB was tested against Sendai virus (Myxovirus para-influenzae 1) in various tissue culture systems. These systems were believed to be most favorable in examining the effect of ABOB for the following reasons. First, production of egg-infectious particles has been proved in the studies of the growth characteristics of Sendai virus in L, HeLa, and FL cells14-16). No such a complete growth has been found with other influenza viruses, which only produce noninfectious hemagglutinins in these cells. Secondly, one-cycle growth of Sendai virus in these tissue culture cells has also been proved14,15). The study on the site of action of antiviral compounds should be done with such a system. Thirdly, in tissue culture studies, the enumerable monolayered cells in closed tubes with the simple medium of definite quantity afford kinetic evaluation of results. A number of tubes can be easily handled in a reproducible manner, and withdrawal of the compound or of the medium can be freely made. This was thought to be most favorable to purse the site of action of the compound in concern.
As a matter of fact, a definite antiviral effect of ABOB was revealed when Sendai virus growth was examined in these tissue culture cells, although the inhibition was not complete. The present paper is chiefly concerned with the effects obtained in S3 clone of Hela cells. The preliminary studies on the site of action of ABOB is also involved.
