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. 1992 Feb;36(2):435–439. doi: 10.1128/aac.36.2.435

Antiviral activities of ribavirin, 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide, and 6'-(R)-6'-C-methylneplanocin A against several ortho- and paramyxoviruses.

S Shigeta 1, S Mori 1, M Baba 1, M Ito 1, K Honzumi 1, K Nakamura 1, H Oshitani 1, Y Numazaki 1, A Matsuda 1, T Obara 1, et al.
PMCID: PMC188453  PMID: 1605607

Abstract

5-Ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR) and 6'-(R)-6'-C-methylneplanocin A (TJ13025) are two novel antiviral agents which are targeted against IMP dehydrogenase and S-adenosylhomocysteine hydrolase, respectively. These compounds have been examined for their activities against various strains of orthomyxoviruses (influenza virus) and paramyxoviruses (parainfluenza virus, mumps virus, measles virus, and respiratory syncytial virus) in vitro. EICAR was 10- to 59-fold more active than ribavirin and TJ13025 was 32- to 330-fold more active than ribavirin against parainfluenza virus types (2 and 3), mumps virus, and measles virus. EICAR was also more active than ribavirin against respiratory syncytial virus and influenza virus, whereas TJ13025 was virtually inactive against these viruses. The 50% virus-inhibitory concentrations of EICAR and TJ13025 were generally within the 0.1- to 1-microgram/ml range. Although the compounds did not prove cytotoxic to stationary host cells (HeLa, Vero, MDCK, and LLCMK2) at a concentration of 200 micrograms/ml, concentrations of 4 to 13 micrograms/ml inhibited the growth of dividing cells. EICAR and TJ13025 should be further pursued as candidate drugs for the treatment of ortho- and paramyxovirus infections.

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Selected References

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  1. Borchardt R. T., Keller B. T., Patel-Thombre U. Neplanocin A. A potent inhibitor of S-adenosylhomocysteine hydrolase and of vaccinia virus multiplication in mouse L929 cells. J Biol Chem. 1984 Apr 10;259(7):4353–4358. [PubMed] [Google Scholar]
  2. 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]
  3. De Clercq E., Cools M., Balzarini J., Snoeck R., Andrei G., Hosoya M., Shigeta S., Ueda T., Minakawa N., Matsuda A. Antiviral activities of 5-ethynyl-1-beta-D-ribofuranosylimidazole-4- carboxamide and related compounds. Antimicrob Agents Chemother. 1991 Apr;35(4):679–684. doi: 10.1128/aac.35.4.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Eriksson B., Helgstrand E., Johansson N. G., Larsson A., Misiorny A., Norén J. O., Philipson L., Stenberg K., Stening G., Stridh S. Inhibition of influenza virus ribonucleic acid polymerase by ribavirin triphosphate. Antimicrob Agents Chemother. 1977 Jun;11(6):946–951. doi: 10.1128/aac.11.6.946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Goswami B. B., Borek E., Sharma O. K., Fujitaki J., Smith R. A. The broad spectrum antiviral agent ribavirin inhibits capping of mRNA. Biochem Biophys Res Commun. 1979 Aug 13;89(3):830–836. doi: 10.1016/0006-291x(79)91853-9. [DOI] [PubMed] [Google Scholar]
  6. Hall C. B., McBride J. T., Walsh E. E., Bell D. M., Gala C. L., Hildreth S., Ten Eyck L. G., Hall W. J. Aerosolized ribavirin treatment of infants with respiratory syncytial viral infection. A randomized double-blind study. N Engl J Med. 1983 Jun 16;308(24):1443–1447. doi: 10.1056/NEJM198306163082403. [DOI] [PubMed] [Google Scholar]
  7. Hosoya M., Shigeta S., Nakamura K., De Clercq E. Inhibitory effect of selected antiviral compounds on measles (SSPE) virus replication in vitro. Antiviral Res. 1989 Sep;12(2):87–97. doi: 10.1016/0166-3542(89)90072-7. [DOI] [PubMed] [Google Scholar]
  8. Kawana F., Shigeta S., Hosoya M., Suzuki H., De Clercq E. Inhibitory effects of antiviral compounds on respiratory syncytial virus replication in vitro. Antimicrob Agents Chemother. 1987 Aug;31(8):1225–1230. doi: 10.1128/aac.31.8.1225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Matsuda A., Minakawa N., Sasaki T., Ueda T. The design, synthesis and antileukemic activity of 5-alkynyl-1-beta-D-ribofuranosylimidazole-4-carboxamides. Chem Pharm Bull (Tokyo) 1988 Jul;36(7):2730–2733. doi: 10.1248/cpb.36.2730. [DOI] [PubMed] [Google Scholar]
  10. Numazaki Y., Shigeta S., Ishida N. Studies on parainfluenza virus infections among infants and children in Sendai. I. Isolation and identification methods of parainfluenza viruses. Jpn J Microbiol. 1968 Sep;12(3):275–281. doi: 10.1111/j.1348-0421.1968.tb00396.x. [DOI] [PubMed] [Google Scholar]
  11. Pauwels R., Balzarini J., Baba M., Snoeck R., Schols D., Herdewijn P., Desmyter J., De Clercq E. Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds. J Virol Methods. 1988 Aug;20(4):309–321. doi: 10.1016/0166-0934(88)90134-6. [DOI] [PubMed] [Google Scholar]
  12. Plotch S. J., Bouloy M., Krug R. M. Transfer of 5'-terminal cap of globin mRNA to influenza viral complementary RNA during transcription in vitro. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1618–1622. doi: 10.1073/pnas.76.4.1618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Plotch S. J., Bouloy M., Ulmanen I., Krug R. M. A unique cap(m7GpppXm)-dependent influenza virion endonuclease cleaves capped RNAs to generate the primers that initiate viral RNA transcription. Cell. 1981 Mar;23(3):847–858. doi: 10.1016/0092-8674(81)90449-9. [DOI] [PubMed] [Google Scholar]
  14. Shigeta S., Konno K., Yokota T., Nakamura K., De Clercq E. Comparative activities of several nucleoside analogs against influenza A, B, and C viruses in vitro. Antimicrob Agents Chemother. 1988 Jun;32(6):906–911. doi: 10.1128/aac.32.6.906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Smee D. F., Matthews T. R. Metabolism of ribavirin in respiratory syncytial virus-infected and uninfected cells. Antimicrob Agents Chemother. 1986 Jul;30(1):117–121. doi: 10.1128/aac.30.1.117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Taber L. H., Knight V., Gilbert B. E., McClung H. W., Wilson S. Z., Norton H. J., Thurson J. M., Gordon W. H., Atmar R. L., Schlaudt W. R. Ribavirin aerosol treatment of bronchiolitis associated with respiratory syncytial virus infection in infants. Pediatrics. 1983 Nov;72(5):613–618. [PubMed] [Google Scholar]
  18. Wilson S. Z., Gilbert B. E., Quarles J. M., Knight V., McClung H. W., Moore R. V., Couch R. B. Treatment of influenza A (H1N1) virus infection with ribavirin aerosol. Antimicrob Agents Chemother. 1984 Aug;26(2):200–203. doi: 10.1128/aac.26.2.200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wray S. K., Gilbert B. E., Knight V. Effect of ribavirin triphosphate on primer generation and elongation during influenza virus transcription in vitro. Antiviral Res. 1985 Feb;5(1):39–48. doi: 10.1016/0166-3542(85)90013-0. [DOI] [PubMed] [Google Scholar]
  20. Wyde P. R., Ambrose M. W., Meyer H. L., Zolinski C. L., Gilbert B. E. Evaluation of the toxicity and antiviral activity of carbocyclic 3-deazaadenosine against respiratory syncytial and parainfluenza type 3 viruses in tissue culture and in cotton rats. Antiviral Res. 1990 Oct-Nov;14(4-5):215–225. doi: 10.1016/0166-3542(90)90003-p. [DOI] [PubMed] [Google Scholar]
  21. de Clercq E., Montgomery J. A. Broad-spectrum antiviral activity of the carbocyclic analog of 3-deazaadenosine. Antiviral Res. 1983 Mar;3(1):17–24. doi: 10.1016/0166-3542(83)90011-6. [DOI] [PubMed] [Google Scholar]

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