Abstract
Modes of action of five antirhinovirus agents were compared. Ro 09-0410, 4',6-dichloroflavan, and RMI-15,731 were active preferentially against human rhinovirus. Serotypes of the virus varied in their susceptibility to these three agents, whereas Ro 09-0179 and enviroxime showed activity against all the serotypes of the virus tested to date. Ro 09-0410, RMI-15,731, and 4',6-dichloroflavan inactivated the virus directly, although 4',6-dichloroflavan did so only slightly. Inactivation by 4',6-dichloroflavan and RMI-15,731 was associated with the binding of the agents to the virus, since the infectivity, reduced by exposure to the agents, was restored to the original level by extraction of the agents with chloroform. The binding of [3H]Ro 09-0410 to human rhinovirus type 2 was inhibited by unlabeled Ro 09-0410, 4',6-dichloroflavan, and RMI-15,731 but not by Ro 09-0179 or enviroxime. Furthermore, subtypes resistant to both 4',6-dichloroflavan and RMI-15,731 showed cross-resistance to Ro 09-0410 and vice versa. On the other hand, sublines resistant to these three agents were not cross-resistant to Ro 09-0179 or enviroxime. These results indicate (i) that Ro 09-0410, 4',6-dichloroflavan, and RMI-15,731 exert their activities through the same mode of action, namely, binding to or interaction with some specific site on the viral capsid protein, and (ii) that the binding or interaction sites for these three agents are either the same or very close to each other.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ash R. J., Parker R. A., Hagan A. C., Mayer G. D. RMI 15,731 (1-[5-tetradecyloxy-2-furanyl]-ethanone), a new antirhinovirus compound. Antimicrob Agents Chemother. 1979 Sep;16(3):301–305. doi: 10.1128/aac.16.3.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bauer D. J., Selway J. W., Batchelor J. F., Tisdale M., Caldwell I. C., Young D. A. 4',6-Dichloroflavan (BW683C), a new anti-rhinovirus compound. Nature. 1981 Jul 23;292(5821):369–370. doi: 10.1038/292369a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DeLong D. C., Reed S. E. Inhibition of rhinovirus replication in in organ culture by a potential antiviral drug. J Infect Dis. 1980 Jan;141(1):87–91. doi: 10.1093/infdis/141.1.87. [DOI] [PubMed] [Google Scholar]
- Ishitsuka H., Ninomiya Y. T., Ohsawa C., Fujiu M., Suhara Y. Direct and specific inactivation of rhinovirus by chalcone Ro 09-0410. Antimicrob Agents Chemother. 1982 Oct;22(4):617–621. doi: 10.1128/aac.22.4.617. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ishitsuka H., Ohsawa C., Ohiwa T., Umeda I., Suhara Y. Antipicornavirus flavone Ro 09-0179. Antimicrob Agents Chemother. 1982 Oct;22(4):611–616. doi: 10.1128/aac.22.4.611. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Korant B. D., Lonberg-Holm K., Yin F. H., Noble-Harvey J. Fractionation of biologically active and inactive populations of human rhinovirus type 2. Virology. 1975 Feb;63(2):384–394. doi: 10.1016/0042-6822(75)90311-6. [DOI] [PubMed] [Google Scholar]
- Lonberg-Holm K., Korant B. D. Early interaction of rhinoviruses with host cells. J Virol. 1972 Jan;9(1):29–40. doi: 10.1128/jvi.9.1.29-40.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lonberg-Holm K., Yin F. H. Antigenic determinants of infective and inactivated human rhinovirus type 2. J Virol. 1973 Jul;12(1):114–123. doi: 10.1128/jvi.12.1.114-123.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Newman J. F., Rowlands D. J., Brown F. A physico-chemical sub-grouping of the mammalian picornaviruses. J Gen Virol. 1973 Feb;18(2):171–180. doi: 10.1099/0022-1317-18-2-171. [DOI] [PubMed] [Google Scholar]
- Ninomiya Y., Ohsawa C., Aoyama M., Umeda I., Suhara Y., Ishitsuka H. Antivirus agent, Ro 09-0410, binds to rhinovirus specifically and stabilizes the virus conformation. Virology. 1984 Apr 30;134(2):269–276. doi: 10.1016/0042-6822(84)90296-4. [DOI] [PubMed] [Google Scholar]
- Stott E. J., Killington R. A. Rhinoviruses. Annu Rev Microbiol. 1972;26:503–524. doi: 10.1146/annurev.mi.26.100172.002443. [DOI] [PubMed] [Google Scholar]
- Wikel J. H., Paget C. J., DeLong D. C., Nelson J. D., Wu C. Y., Paschal J. W., Dinner A., Templeton R. J., Chaney M. O., Jones N. D. Synthesis of syn and anti isomers of 6-[[(hydroxyimino)phenyl]methyl]-1-[(1-methylethyl)sulfonyl]-1H-benzimidazol-2-amine. Inhibitors of rhinovirus multiplication. J Med Chem. 1980 Apr;23(4):368–372. doi: 10.1021/jm00178a004. [DOI] [PubMed] [Google Scholar]