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Comparative activity of selected antiviral compounds against clinical isolates of human cytomegalovirus

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Abstract

Seventeen fresh clinical isolates of human cytomegalovirus (HCMV) were examined for their in vitro susceptibility to different potential anti-HCMV drugs, including a series of acyclic nucleoside phosphonate analogues as well as the reference compounds ganciclovir, foscarnet and acyclovir. Three sulfated polysaccharides (heparin, dextran sulfate and pentosan polysulfate) known for their ability to inhibit adsorption of enveloped viruses to the cells were also included in these comparative tests. Of the reference compounds, ganciclovir was the most potent. However, it was about five-fold less potent than the phosphonate derivative (s)-1-(3-hydroxy-2-phosphonylmethoxy-propyl)cytosine (HPMPC) and its cyclic form (cHPMPC). All test compounds, including the sulfated polysaccharides, were as active against the clinical isolates as they were against the laboratory strains of HCMV. Furthermore, the choice of the cell line (HEL or MRC-5) did not influence the anti-HCMV activity of the compounds.

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References

  1. Erice A, Jordan MC, Chace BA, Fletcher C, Chinnock BJ, Balfour HH Ganciclovir treatment of cytomegalovirus disease in transplant recipients and other immunocompromised hosts. Journal of the American Medical Association 1987, 257: 3082–3087.

    PubMed  Google Scholar 

  2. Tyms AS, Taylor DL, Parkin JM Cytomegalovirus and the acquired immunodeficiency syndrome. Journal of Antimicrobial Chemotherapy 1989, 23, Supplement A: 89–105.

    Google Scholar 

  3. Verheyden JPH Evolution of therapy for cytomegalovirus infection. Reviews of Infectious Diseases 1988, 10, Supplement 3: 477–489.

    Google Scholar 

  4. Klintmalm G, Lonnqvist B, Öberg B, Gahrton G, Lernestedt JO, Lundgren G, Ringden O, Robert KH, Wahren B, Groth CG Intravenous foscarnet for the treatment of severe cytomegalovirus infection in allograft recipients. Scandinavian Journal of Infectious Diseases 1985, 17: 157–163.

    PubMed  Google Scholar 

  5. Laskin OL, Stahl-Bayliss CM, Kalman CM, Rosecan LR Use of ganciclovir to treat serious cytomegalovirus infections in patients with AIDS. Journal of Infectious Diseases 1987, 155: 323–327.

    PubMed  Google Scholar 

  6. Reed EC, Bowden RA, Dandliker PS, Lilleby KE, Meyers JD Treatment of cytomegalovirus pneumonia with ganciclovir and intravenous cytomegalovirus immunoglobulin in patients with bone marrow transplants. Annals of Internal Medicine 1988, 109: 783–788.

    PubMed  Google Scholar 

  7. Milliken S, Powles R, Ettinger N, Gallagher C, Jameson B, Tryhorn Y, Stern H, Selby P Ganciclovir in the treatment of cytomegalovirus pneumonitis in bone marrow transplant recipients. Transplantation Proceedings 1989, 21: 3110–3111.

    PubMed  Google Scholar 

  8. Emanuel D Treatment of cytomegalovirus disease. Seminars in Hematology 1990, 27: 22–27.

    PubMed  Google Scholar 

  9. Kaplan CS, Petersen EA, Icenogle TB, Copeland JG, Villar HV, Sampliner R, Minnich L, Ray G Gastrointestinal cytomegalovirus infection in heart and heart-lung transplant recipients. Archives of Internal Medicine 1989, 149: 2095–2100.

    PubMed  Google Scholar 

  10. Youle M, Chanas A, Gazzard B Treatment of acquired immune deficiency syndrome related pneumonitis with foscarnet: a double-blind placebo controlled study. Journal of Infection 1990, 20: 41–50.

    PubMed  Google Scholar 

  11. Prentice HG Prophylaxis and treatment of cytomegalovirus infections in the bone marrow transplant recipient. Journal of Antimicrobial Chemotherapy 1989, 23, Supplement E: 23–30.

    PubMed  Google Scholar 

  12. De Clercq E, Holý A, Rosenberg I, Sakuma T, Balzarini J, Maudgal PC A novel selective broadspectrum anti-DNA virus agent. Nature 1986, 323: 464–467.

    PubMed  Google Scholar 

  13. De Clercq E, Sakuma T, Baba M, Pauwels R, Balzarini J, Rosenberg I, Holý A Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines. Antiviral Research 1987, 8: 261–272.

    PubMed  Google Scholar 

  14. Snoeck R, Sakuma T, De Clercq E, Rosenberg I, Holý A (S)-1-(3-Hydroxy-2-phosphonylmethoxypropyl)cytosine, a potent and selective inhibitor of human cytomegalovirus replication. Antimicrobial Agents and Chemotherapy 1988, 32: 1839–1844.

    PubMed  Google Scholar 

  15. Neyts J, Snoeck R, Schols D, Balzarini J, De Clercq E Selective inhibition of human cytomegalovirus DNA synthesis by (S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl)-cytosine [(S)-HPMPC] and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG). Virology 1990, 179: 41–50.

    PubMed  Google Scholar 

  16. Snoeck R, Schols D, Andrei G, Neyts J, De Clercq E Antiviral activity of anti-cytomegalovirus agents (HPMPC, HPMPA) assessed by a flow cytometric method and DNA hybridization technique. Antiviral Research 1991, 16: 1–9.

    PubMed  Google Scholar 

  17. Baba M, Snoeck R, Pauwels R, De Clercq E Sulfated polysaccharides are potent and selective inhibitors of various enveloped viruses, including herpes simplex virus, cytomegalovirus, vesicular stomatitis virus and human immunodeficiency virus. Antimicrobial Agents and Chemotherapy 1988, 32: 1742–1745.

    PubMed  Google Scholar 

  18. Witvrouw M, Schols D, Andrei G, Snoeck R, Pauwels R, Balzarini J, De Clercq E Antiviral activity of low-MW dextran sulphate (derived from dextran MW 1000) compared with dextran sulphate samples of higher MW. Antiviral Chemistry and Chemotherapy 1991, 2: 171–179.

    Google Scholar 

  19. Amadei C, Tardy-Panit M, Couillin P, Coulon M, Cabau N, Boué A, Michelson S Kinetic study of the development and localization of human cytomegalovirus-induced antigens using monoclonal antibodies. Annales de Virologie (Institut Pasteur) 1983, 134E: 165–180.

    Google Scholar 

  20. Schols D, Snoeck R, Neyts J, De Clercq E Detection of immediate early, early and late antigens of human cytomegalovirus by flow cytometry. Journal of Virological Methods 1989, 26: 247–254.

    PubMed  Google Scholar 

  21. Pauwels R, Balzarini J, Schols D, Baba M, Desmyter J, Rosenberg I, Holý A, De Clercq E Phosphonylmethoxyethyl purine derivatives, a new class of antihuman immunodeficiency virus agents. Antimicrobial Agents and Chemotherapy 1988, 32: 1025–1030.

    PubMed  Google Scholar 

  22. Balzarini J, Naesens L, De Clercq E Anti-retrovirus activity of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) in vivo increases when it is less frequently administered. International Journal of Cancer 1990, 46: 337–340.

    Google Scholar 

  23. Snoeck R, Lagneaux L, Delforge A, Bron D, Van der Auwera P, Stryckmans P, Balzarini J, De Clercq E Inhibitory effects of potent inhibitors of human immunodeficiency virus and cytomegalovirus on the growth of human granulocyte-macrophage progenitor cells in vitro. European Journal of Clinical Microbiology & Infectious Diseases 1990, 9: 615–619.

    Google Scholar 

  24. De Clercq E, Holý A, Rosenberg I Efficacy of phosphonylmethoxyalkyl derivatives of adenine in experimental herpes simplex virus and vaccinia virus infections in vivo. Antimicrobial Agents and Chemotherapy 1989, 33: 185–191.

    PubMed  Google Scholar 

  25. De Clercq E, Holý A Efficacy of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine in various models of herpes simplex virus infection in mice. Antimicrobial Agents and Chemotherapy 1991, 35: 701–706.

    PubMed  Google Scholar 

  26. Biron KK, Fyfe JA, Stanat SC, Leslie LK, Sorrell JB, Lambe CU, Coen DM A human cytomegalovirus mutant resistant to the nucleoside analog 9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine (BW B759U) induces reduced levels of BW B759U triphosphate. Proceedings of the National Academy of Sciences of the USA 1986, 83: 8769–8773.

    PubMed  Google Scholar 

  27. Erice A, Chou S, Biron KK, Stanat SC, Balfour HH Jr, Jordan MC Progressive disease due to ganciclovir-resistant cytomegalovirus in immunocompromised patients. New England Journal of Medicine 1989, 320: 289–293.

    PubMed  Google Scholar 

  28. Meyers JD, Reed EC, Shepp DH, Thornquist M, Dandliker PS, Vicary CA, Flournoy N, Kirk LE, Kersey JH, Thomas ED, Balfour HH Jr Acyclovir for prevention of cytomegalovirus infection and disease after allogeneic marrow transplantation. New England Journal of Medicine 1988, 318: 70–75.

    PubMed  Google Scholar 

  29. Plotkin SA, Drew WL, Felsenstein D, Hirsch MS Sensitivity of clinical isolates of human cytomegalovirus to 9-(1,3-dihydroxy-2-propoxymethyl)guanine. Journal of Infectious Diseases 1985, 152: 833–834.

    PubMed  Google Scholar 

  30. Baba M, De Clercq E, Schols D, Pauwels R, Snoeck R, Van Boeckel C, Van Dedem G, Kraaijeveld N, Hobbelen P, Ottenheijm H, Den Hollander F Novel sulfated polysaccharides: dissociation of anti-human immunodeficiency virus activity from antithrombin activity. Journal of Infectious Diseases 1990, 161: 208–213.

    PubMed  Google Scholar 

  31. Abrams DI, Kuno S, Wong R, Jeffords K, Nash M, Molaghan JB, Gorter R, Ueno R Oral dextran sulfate (UA001) in the treatment of the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. Annals of Internal Medicine 1989, 110: 183–188.

    PubMed  Google Scholar 

  32. Lorentsen KJ, Hendrix CW, Collins JM, Kornhauser DM, Petty BG, Klecker RW, Flexner C, Eckel RH, Lietman PS Dextran sulfate is poorly absorbed after oral administration. Annals of Internal Medicine 1989, 111: 561–566.

    PubMed  Google Scholar 

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Andrei, G., Snoeck, R., Schols, D. et al. Comparative activity of selected antiviral compounds against clinical isolates of human cytomegalovirus. Eur. J. Clin. Microbiol. Infect. Dis. 10, 1026–1033 (1991). https://doi.org/10.1007/BF01984924

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