Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1986 Mar;29(3):482–487. doi: 10.1128/aac.29.3.482

Antirhinovirus activity of purine nucleoside analogs.

E De Clercq, R Bernaerts, D E Bergstrom, M J Robins, J A Montgomery, A Holy
PMCID: PMC180418  PMID: 3013084

Abstract

A wide variety of purine nucleoside (mainly tubercidin and adenosine) analogs, which had previously been shown to inhibit the replication of a broad spectrum of RNA viruses, were evaluated for their antirhinovirus activity in human diploid (WI-38) fibroblasts. Tubercidin, 5-(1-hydroxyethyl)tubercidin, 5-(2-buten-1-yl)tubercidin, toyocamycin, and sangivamycin emerged as the most potent inhibitors. These compounds inhibited the replication of rhinovirus types 1A, 1B, and 9 at an MIC well below 1 microgram/ml. However, these compounds proved cytotoxic for the uninfected host cells at concentrations which were only slightly higher (3- to 10-fold, on the average) than those required for inhibition of rhinovirus replication. The most selective inhibitor of rhinovirus replication was 3-deazaguanine, with a selectivity index of 50. None of the carbocyclic and acyclic analogs of adenosine tested exhibited a potent or selective antirhinovirus activity.

Full text

PDF
482

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allen L. B., Huffman J. H., Dan Cook P., Meyer R. B., Jr, Robins R. K., Sidwell R. W. Antiviral activity of 3-deazaguanine, 3-deazaguanosine, and 3-deazaguanylic acid. Antimicrob Agents Chemother. 1977 Jul;12(1):114–119. doi: 10.1128/aac.12.1.114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Bergstrom D. E., Brattesani A. J., Ogawa M. K., Reddy P. A., Schweickert M. J., Balzarini J., De Clercq E. Antiviral activity of C-5 substituted tubercidin analogues. J Med Chem. 1984 Mar;27(3):285–292. doi: 10.1021/jm00369a010. [DOI] [PubMed] [Google Scholar]
  5. Bucknall R. A., Swallow D. L., Moores H., Harrad J. A novel substituted guanidine with high activity in vitro against rhinoviruses. Nature. 1973 Nov 16;246(5429):144–145. doi: 10.1038/246144a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cadman E. C., Dix D. E., Handschumacher R. E. Clinical, biological, and biochemical effect of pyrazofurin. Cancer Res. 1978 Mar;38(3):682–688. [PubMed] [Google Scholar]
  7. De Clercq E. Antiviral and antimetabolic activities of neplanocins. Antimicrob Agents Chemother. 1985 Jul;28(1):84–89. doi: 10.1128/aac.28.1.84. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. De Clercq E., Bergstrom D. E., Holy A., Montgomery J. A. Broad-spectrum antiviral activity of adenosine analogues. Antiviral Res. 1984 Jun;4(3):119–133. doi: 10.1016/0166-3542(84)90012-3. [DOI] [PubMed] [Google Scholar]
  9. De Clercq E., Cools M. Antiviral potency of adenosine analogues: correlation with inhibition of S-adenosylhomocysteine hydrolase. Biochem Biophys Res Commun. 1985 May 31;129(1):306–311. doi: 10.1016/0006-291x(85)91438-x. [DOI] [PubMed] [Google Scholar]
  10. De Clercq E., Holý A. Alkyl esters of 3-adenin-9-yl-2-hydroxypropanoic acid: a new class of broad-spectrum antiviral agents. J Med Chem. 1985 Mar;28(3):282–287. doi: 10.1021/jm00381a004. [DOI] [PubMed] [Google Scholar]
  11. De Clercq E., Walker R. T. Synthesis and antiviral properties of 5-vinylpyrimidine nucleoside analogs. Pharmacol Ther. 1984;26(1):1–44. doi: 10.1016/0163-7258(84)90049-4. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Diana G. D., Carabateas P. M., Johnson R. E., Williams G. L., Pancic F., Collins J. C. Antiviral activity of some beta-diketones. 4. Benzyl diketones. In vitro activity against both RNA and DNA viruses. J Med Chem. 1978 Sep;21(9):889–894. doi: 10.1021/jm00207a010. [DOI] [PubMed] [Google Scholar]
  14. Diana G. D., McKinlay M. A., Brisson C. J., Zalay E. S., Miralles J. V., Salvador U. J. Isoxazoles with antipicornavirus activity. J Med Chem. 1985 Jun;28(6):748–752. doi: 10.1021/jm00383a010. [DOI] [PubMed] [Google Scholar]
  15. Diana G. D., Salvador U. J., Zalay E. S., Carabateas P. M., Williams G. L., Collins J. C., Pancic F. Antiviral activity of some beta-diketones. 2. Aryloxy alkyl diketones. In vitro activity against both RNA and DNA viruses. J Med Chem. 1977 Jun;20(6):757–761. doi: 10.1021/jm00216a004. [DOI] [PubMed] [Google Scholar]
  16. Diana G. D., Salvador U. J., Zalay E. S., Johnson R. E., Collins J. C., Johnson D., Hinshaw W. B., Lorenz R. R., Thielking W. H., Pancic F. Antiviral activity of some beta-diketones. 1. Aryl alkyl diketones. In vitro activity against both RNA and DNA viruses. J Med Chem. 1977 Jun;20(6):750–756. doi: 10.1021/jm00216a003. [DOI] [PubMed] [Google Scholar]
  17. Galabov A. S., Velichkova E. H., Vassilev G. N. Antirival activity of N-phenyl-N'-arylthiourea derivatives against some Rhinoviruses. Chemotherapy. 1977;23(2):81–89. doi: 10.1159/000221975. [DOI] [PubMed] [Google Scholar]
  18. Giziewicz J., De Clercq E., Luczak M., Shugar D. Antiviral and antimetabolic activities of formycin and its N1-, N2-, 2'-O- and 3'-O-methylated derivatives. Biochem Pharmacol. 1975 Oct 1;24(19):1813–1817. doi: 10.1016/0006-2952(75)90462-1. [DOI] [PubMed] [Google Scholar]
  19. Gladych J. M., Hunt J. H., Jack D., Haff R. F., Boyle J. J., Stewart R. C., Ferlauto R. J. Inhibition of rhinovirus by isatin thiosemicarbazone analogues. Nature. 1969 Jan 18;221(5177):286–287. doi: 10.1038/221286b0. [DOI] [PubMed] [Google Scholar]
  20. Hayden F. G., Gwaltney J. M., Jr Prophylactic activity of intranasal enviroxime against experimentally induced rhinovirus type 39 infection. Antimicrob Agents Chemother. 1982 Jun;21(6):892–897. doi: 10.1128/aac.21.6.892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Huffman J. H., Sidwell R. W., Khare G. P., Witkowski J. T., Allen L. B., Robins R. K. In vitro effect of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (virazole, ICN 1229) on deoxyribonucleic acid and ribonucleic acid viruses. Antimicrob Agents Chemother. 1973 Feb;3(2):235–241. doi: 10.1128/aac.3.2.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. 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]
  24. Levandowski R. A., Pachucki C. T., Rubenis M., Jackson G. G. Topical enviroxime against rhinovirus infection. Antimicrob Agents Chemother. 1982 Dec;22(6):1004–1007. doi: 10.1128/aac.22.6.1004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Matsumoto S., Stanfield F. J., Goore M. Y., Haff R. F. The antiviral activity of a triazinoindole (SK&F 30097). Proc Soc Exp Biol Med. 1972 Feb;139(2):455–460. doi: 10.3181/00379727-139-36163. [DOI] [PubMed] [Google Scholar]
  26. Miller F. D., Monto A. S., DeLong D. C., Exelby A., Bryan E. R., Srivastava S. Controlled trial of enviroxime against natural rhinovirus infections in a community. Antimicrob Agents Chemother. 1985 Jan;27(1):102–106. doi: 10.1128/aac.27.1.102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. Ohnishi H., Yamaguchi K., Shimada S., Himuro S., Suzuki Y. Antiviral activity of sodium 5-aminosulfonyl-2,4-dichlorobenzoate (M12325). Antimicrob Agents Chemother. 1982 Aug;22(2):250–254. doi: 10.1128/aac.22.2.250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Otto M. J., Fox M. P., Fancher M. J., Kuhrt M. F., Diana G. D., McKinlay M. A. In vitro activity of WIN 51711, a new broad-spectrum antipicornavirus drug. Antimicrob Agents Chemother. 1985 Jun;27(6):883–886. doi: 10.1128/aac.27.6.883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Phillpotts R. J., Wallace J., Tyrrell D. A., Freestone D. S., Shepherd W. M. Failure of oral 4',6-dichloroflavan to protect against rhinovirus infection in man. Arch Virol. 1983;75(1-2):115–121. doi: 10.1007/BF01314131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Phillpotts R. J., Wallace J., Tyrrell D. A., Tagart V. B. Therapeutic activity of enviroxime against rhinovirus infection in volunteers. Antimicrob Agents Chemother. 1983 May;23(5):671–675. doi: 10.1128/aac.23.5.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Powers R. D., Gwaltney J. M., Jr, Hayden F. G. Activity of 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile (MDL-860) against picornaviruses in vitro. Antimicrob Agents Chemother. 1982 Oct;22(4):639–642. doi: 10.1128/aac.22.4.639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Reed S. E., Bynoe M. L. The antiviral activity of isoquinoline drugs for rhinoviruses in vitro and in vivo. J Med Microbiol. 1970 May;3(2):346–352. doi: 10.1099/00222615-3-2-346. [DOI] [PubMed] [Google Scholar]
  34. Revankar G. R., Gupta P. K., Adams A. D., Dalley N. K., McKernan P. A., Cook P. D., Canonico P. G., Robins R. K. Synthesis and antiviral/antitumor activities of certain 3-deazaguanine nucleosides and nucleotides. J Med Chem. 1984 Nov;27(11):1389–1396. doi: 10.1021/jm00377a002. [DOI] [PubMed] [Google Scholar]
  35. Schneller S. W., Luo J. K., Hosmane R. S., De Clercq E., Stoeckler J. D., Agarwal K. C., Parks R. E., Jr, Saunders P. P. Synthesis and biological evaluation of 6-amino-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (3,7-dideazaguanine). J Med Chem. 1984 Dec;27(12):1737–1739. doi: 10.1021/jm00378a037. [DOI] [PubMed] [Google Scholar]
  36. Streeter D. G., Witkowski J. T., Khare G. P., Sidwell R. W., Bauer R. J., Robins R. K., Simon L. N. Mechanism of action of 1- -D-ribofuranosyl-1,2,4-triazole-3-carboxamide (Virazole), a new broad-spectrum antiviral agent. Proc Natl Acad Sci U S A. 1973 Apr;70(4):1174–1178. doi: 10.1073/pnas.70.4.1174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Tisdale M., Selway J. W. Inhibition of an early stage of rhinovirus replication by dichloroflavan (BW683C). J Gen Virol. 1983 Apr;64(Pt 4):795–803. doi: 10.1099/0022-1317-64-4-795. [DOI] [PubMed] [Google Scholar]
  38. Togo Y., Schwartz A. R., Hornick R. B. Antiviral effect of 3, 4-dihydro-1-isoquinolineacetamide hydrochloride in experimental human rhinovirus infection. Antimicrob Agents Chemother. 1973 Dec;4(6):612–616. doi: 10.1128/aac.4.6.612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Torney H. L., Dulworth J. K., Steward D. L. Antiviral activity and mechanism of action of 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile (MDL-860). Antimicrob Agents Chemother. 1982 Oct;22(4):635–638. doi: 10.1128/aac.22.4.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Watanabe K. A., Su T. L., Klein R. S., Chu C. K., Matsuda A., Chun M. W., Lopez C., Fox J. J. Nucleosides. 123. Synthesis of antiviral nucleosides: 5-substituted 1-(2-deoxy-2-halogeno-beta-D-arabinofuranosyl)cytosines and -uracils. Some structure-activity relationships. J Med Chem. 1983 Feb;26(2):152–156. doi: 10.1021/jm00356a007. [DOI] [PubMed] [Google Scholar]
  41. Zerial A., Werner G. H., Phillpotts R. J., Willmann J. S., Higgins P. G., Tyrrell D. A. Studies on 44 081 R.P., a new antirhinovirus compound, in cell cultures and in volunteers. Antimicrob Agents Chemother. 1985 May;27(5):846–850. doi: 10.1128/aac.27.5.846. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES