Biopolym. Cell. 2004; 20(4):337-342.
Inhibitory effect of 6-azacytidine on human cytomegalovirus infection in cellular system
1Abdullaeva M. V., 1Frolov A. F., 2Alexeeva I. V., 2Palchykovskaja L. I., 3Fedorova N. E.
  1. Gromashevsky L.V. Institute of Epidemiology and Infection Diseases, AMS of Ukraine
    5, Amosova Str., Kyiv, Ukraine, 03038
  2. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  3. D. I. Ivanovsky Institute of Virology, Russian Academy of Medical Sciences
    16, Gamalei Str., Moscow, Russian Federation


Effects of a modified nucleoside analog 6-Azacytidine (2-b-D-ribofuranosyl-5-amino-1,2,4-triazin-3(2H)-one) on cytomegalovirus (CMV) infection in vitro, have been studied. 6-AZC inhibits the CMV cytopathic action, the effective dose of 6-AZC being 0.005 mg/ml. The analysis of cell viability, growth characteristics, and DNA synthesis has revealed that the cytotoxic effect of 6-AZC in human diploid fibroblasts is negligible. The cytotoxicity index range is 2.4 to 24 mg/ml when tested by different methods. The selectivity index of 6-AZC is 48-480, which differs negligibly from that of gancyclovir (100-1000), while the cytotoxicity of 6-AZC is essentially lower. The immunocytochemical analysis of virus proteins in the infected cells has shown that 6-AZC inhibits the production of late structural CMV protein gB, but does not influence the expression of early nonstructural protein pp72 and early protein p65.


[1] De Clercq E. Targets for the antiviral activity of pyrimidine and purine nucleoside analogues. Nucleosides and Nucleotides. 1987; 6(1-2):197-207.
[2] Kraevskii AA. Molecular bases in the search for drugs for treating AIDS. Achievements and possible prospects. Mol Biol (Mosk). 1999;33(3):343-52.
[3] Cheng YC. L-Nucleoside analogues against cancer-causing viruses have potential in the prevention, delayed onset and treatment of viral associated cancers. Antivir Chem Chemother. 2001;12 Suppl 1:5-11.
[4] Bektemirov TA, Lintskaia GL, Chernetskii VP, Galegov GA. The inhibiting effect of 6-azacytidine on reproduction of smallpox virus in tissue culture. Vopr Med Khim. 1974;20(1):50-1.
[5] Nosach LN, Butenko SI, Timofeeva MIa, Diachenko NS, Tikhomirova TP. [An analysis of the DNA synthesized in adenovirus-infected cells under exposure to nucleoside analogs]. Mikrobiol Zh. 1989;51(6):73-5. Russian.
[6] Nosach LN, Dyachenko NS, Shalamay AS, Alekseeva IV, Kushko L Ya, Ozvinchuk II, Zhovnovataya VL, Butenko SL, Petrovskaya IA, Drannik GN. Antiadenovirus and immunostimulating actions of 6-azacylidine. Biopolym. Cell. 1996; 12(1):75-85
[7] Frolov AF, Radolitskaya LS, Chernetskiy VYa. Action anomalous nucleosides on experimental influenza infection of white mice. Viruses and virus diseases: Resp. Sat. Kyiv, 1986; Iss. 14:3-6.
[8] Dyachenko N, Rybalko S, Nosach L, Alexeeva I, Shalamay A. Antiadenovirus and anti-herpes activity of 6-azacytidine. 12th Int. Conf. on Antiviral Res. Int. Soc. for Antiviral Res. (March 21-25, 1999). Jerusalem, 1999:87.
[9] Starcheus AP, Chernetski? VP. [Effect of 6-azauridine, 6-azacytidine and 8-azaguanine on reproduction of IV type adenovirus in a tissue culture]. Mikrobiol Zh. 1967;29(2):157-60. Ukrainian.
[10] Petrusha NA. Toxico-pharmacological properties of 6-azacytidine. Farmakol Toksikol. 1987;50(2):75-6.
[11] Fedorova NE, Adueva SM, Medzhidova AA, Romanova VS, Parnes ZN, Galegov GA, Kushch AA. Suppression of cytomegalovirus infection in cell system by fullerene amino acid derivates. Vopr Virusol. 2002;47(1):30-4.
[12] Clyde S, Crumpacker MD. Ganciclovir. New England J Med. 1996; 335(10):721-9.
[13] Erice A. Resistance of human cytomegalovirus to antiviral drugs. Clin Microbiol Rev. 1999; 12(2):286-97.
[14] Mar EC, Cheng YC, Huang ES. Effect of 9-(1,3-dihydroxy-2-propoxymethyl) guanine on human cytomegalovirus replication in vitro. Antimicrob Agents Chemother. 1983; 24(4):518-21.
[15] Alexeeva I, Dyachenko N, Nosach L, Zhovnovataya V, Rybalko S, Lozitskaya R, Fedchuk A, Lozitsky V, Gridina T, Shalamay A, Palchikovskaja L, Povnitsa O. 6-azacytidine - compound with wide spectrum of antiviral activity. Nucleosides Nucleotides Nucleic Acids. 2001; 20(4-7):1147-52.
[16] Samijlenko SP, Alexeeva IV, Palchykivs'ka LH, Kondratyuk IV, Stepanyugin AV, Shalamay AS, Hovorun DM. Structural features of 6-azacytidine and its derivatives: data of NMR and IR spectroscopies. Biopolym Cell. 1997; 13(6):445-52.
[17] Yepifanova OI. Lectures on the cell cycle. Moscow, 1997; 144 p.
[18] Makarova NE, Kushch AA, Ivanova LA, Martynova VN, Barinskii IF, Pustowoit B. Preparation of monoclonal antibodies to super early human cytomegalovirus proteins and their use for detecting infected cells. Vopr Virusol. 1996;41(1):28-32.
[19] Snoeck R, Neyts J, De Clerq E. Strategies for the treatment of cytomegalovirus infection. Multidisciplinary approach to understanding cytomegalovirus disease: proceedings of the Fourth Int. Cytomegalovirus Workshop: multidisciplinary approaches to understanding CMV disease, Paris, France, 19-21 April 1993. Eds S. Michelson, S. A. Plotkin. Amsterdam, 1993: 269-78.
[20] Webster A. Cytomegalovirus as a possible cofactor in HIV disease progression. J Acquir Immune Defic Syndr. 1991;4 Suppl 1:S47-52.