Download PDF
Drug Res (Stuttg) 2017; 67(10): 583-590
DOI: 10.1055/s-0043-111014
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Inhibitory Effect of Abitylguanide on Adenovirus Replication

Angel S. Galabov
1   Department of Virology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia
,
Vesselina Vassileva
2   Electron microscopy, Medical Academy, Sofia, Bulgaria
,
Vera Karabasheva
2   Electron microscopy, Medical Academy, Sofia, Bulgaria
› Author Affiliations
Further Information

Publication History

received 09 February 2017

accepted 08 May 2017

Publication Date:
06 June 2017 (online)

Also available at
    Permissions and Reprints

Abstract

N’N’-anhydro-bis(β-hydroxy-ethyl)biguanide.HCl (abitylguanide) demonstrated a marked inhibitory effect on replication in cell cultures of a broad spectrum of human adenoviruses both standard laboratory strains and strains isolated from epidemic keratoconjunctivitis patients. The strongest inhibitory activity was found in viruses belonging to subgroup C (Rosen’s subgroup III). The compound susceptible period of human adenovirus 5 replication in primary cell cultures of human embryo kidney cells included the total replication cycle and was especially pronounced during the exponential phase of the virus growth curve. Electron microscopy established that the compound decreased the percentage of cells in which mature or empty virions with the characteristic nuclear localization were observed; a complete absence of paracrystals was registered and the number of cells with virus particles arranged in crystals in the nucleoplasm was strongly decreased. Abitylguanide can be considered as a ligand of adenovirus capsid protein(s).

Key words

abitylguanide - human adenoviruses - electron microscopy
 

  • References

  • 1 Wadell G, Allard A, Johansson M. et al. Enteric adenoviruses. Ciba Foundation Symposium. 1987; 128: 63-91
    PubMedGoogle Scholar
  • 2 Liu L, Qian Y, Zhang Y. et al. Adenoviruses associated with acute diarrhea in children in Beijing, China. PLoS One 2014; 9: e88791
    CrossrefPubMedGoogle Scholar
  • 3 Echavarria M. Adenoviruses in immunocompromised hosts. Clin Microbiol Rev 2008; 21: 704-715
    Google Scholar
  • 4 Jin X, Ishiko H, Nata NT. Molecular epidemiology of adenoviral conjunctivitis in Hanoi, Vietnam. Am J Ophthalmol 2006; 113: 1064-1066
    PubMedGoogle Scholar
  • 5 Butt AL, Chodosh J. Adenoviral keratoconjunctivitis in a tertiary care eye clinic. Cornea 2006; 25: 199-202
    CrossrefPubMedGoogle Scholar
  • 6 Sambursky RP, Fram N, Cohen EJ. The prevalence of adenoviral conjunctivitis at the Wille Eye Hospital emergency room. Optometry 2007; 78: 236-239
    CrossrefPubMedGoogle Scholar
  • 7 Bialansiewicz A. Adenoviral keratoconjunctivitis. Sultan Qaboos Univ Med J 2007; 7: 15-23
    PubMedGoogle Scholar
  • 8 Pihos AM. Epidemic keratoconjunctivitis: A review of current concepts in management. J Optom 2013; 6: 69-74
    CrossrefPubMedGoogle Scholar
  • 9 Tabbara KF, Jarade EF. Ganciclovir effects in adenoviral keratoconjunctivitis. [abstracts 3111-B253] ARVO 2001; 42: S579
    PubMedGoogle Scholar
  • 10 Kinchington PR, Romanowski EG, Gordon YJ. Prospects for adenovirus antivirals. J Antimicrob Chemother 2005; 55: 424-429
    CrossrefPubMedGoogle Scholar
  • 11 Throusdale MD, Goldschmidt PL, Nobrega R. Activity of ganciclovir against human adenovirus type-5 infection in cell culture and cotton rat eyes. Cornea 1994; 13: 435-439
    CrossrefPubMedGoogle Scholar
  • 12 Isenberg SJ, Apt L, Valenton M. A controlled trial of povidone-iodine to treat infectious conjunctivitis in children. Am J Ophthalmol 2002; 134: 681-688
    CrossrefPubMedGoogle Scholar
  • 13 de Oliveira CB, Stevenson D, LaBree L. et al. Evaluation of cidofovir (HPMPC, GS-504) against adenovirus type 5 infection in vitro and in a New Zealand rabbit ocular model. Antiviral Res 1996; 31: 165-172
    CrossrefPubMedGoogle Scholar
  • 14 Romanowski EG, Gordon YI. Efficacy of topical cidofovir on multiple adenoviral serotypes in the New Zealand rabbit ocular model. Invest Ophthalm & Vis Sci 2000; 41: 460-463
    PubMedGoogle Scholar
  • 15 Hillenkamp J, Reinhard T, Ross RS. et al. The effect of cidofovir 1% with and without cyclosporine a 1% as a topical treatment of acute adenoviral keratoconjunctivitis: A controlled clinical pilot study. Ophthalmology 2002; 109: 845-850
    CrossrefPubMedGoogle Scholar
  • 16 Greber UF, Arnberg N, Wadel N. et al. Adenoviruses: From pathogens to therapeutics. 10th International Adenovirus Meeting. Cellular Microbiology 2013; 15: 16-23
    CrossrefPubMedGoogle Scholar
  • 17 Öberg CT, Strand M, Andersson EK. et al. Synthesis, biological evaluation and structure-activity relationship of 2-[2-(benzoylamino)benzoylamino] benzoic acid analogues as inhibitors of adenovirus replication. J Medic Chemistry 2012; 55: 3170-3181
    PubMedGoogle Scholar
  • 18 Galabov A, Vilaginès R. Action du chlorhydrate de N’N’anhydro-bis (β-hydroxy-ethyl) biguanide (ABOB) sur le développement du virus de l’herpès en culture de tissu. Arch Ges Virusforsch 1970; 31: 183-190
    CrossrefPubMedGoogle Scholar
  • 19 Galabov A, Vilaginès R. Action of N’N’anhydrobis (β-hydroxyethyl) biguanide (ABOB) on the DNA synthesis of herpes simplex virus. C r Acad Bulg Sci 1971; 24: 119-121
    PubMedGoogle Scholar
  • 20 Rénard G, Dhermy P. Étude clinique et expérimentales de l’herpès de la cornée et de son traitement par un virostatique nouveau ABOB (Virustat). Sém Hôp (Paris) 1963; 39: 1250
    PubMedGoogle Scholar
  • 21 Galabov AS. N,N’-Disubstituted thioureas and abitylguanide – specific viral inhibitors. DSc Dissertation These, Medical Academy, Sofia. 1978;
    PubMed
  • 22 Duluc J, Labouche F. Premiers résultats obtenues dans le traitement de quelques dermatoses par le 1022 Y. D, (ABOB). Bull Soc Franc Dermat & Sypb 1962; 69: 539
    PubMedGoogle Scholar
  • 23 Rivoire MJ. Action du chlorhydrate de N’N’ anhydro-bis (β-hydroxyethyl) biguanide sur certaines affections dermatologiques d’origine virale. Lyon Médical 1965; 6: 323
    PubMedGoogle Scholar
  • 24 Longchamps J. A propos de quelques résultats cliniques d’un nouveau médicament anti-viral. Journ Méd Chir Prat 1963; 134: 107
    PubMedGoogle Scholar
  • 25 Sjöberg B. Experiments on prophylaxis and suppression of epidemic influenza with N’N’-anhydrobis-(β-hydroxyethyl)biguanide-hydrochloride (ABOB). A double blind study. Antib Med Clin Therapy 1960; 7: 97-102
    PubMedGoogle Scholar
  • 26 Cutting WC. Antifertility effects of biguanides. Antibiot & Chemotherapy (Northfield) 1962; 12: 671-675
    PubMedGoogle Scholar
  • 27 Wassileva PIv, Galabov AS. Über die Behandlung der epidemischen Keratokonjunktivitis mit ABOB. Klinische und Laboruntersuchungen. Klin Mbl Augenheilk 1975; 166: 77-83
    PubMedGoogle Scholar
  • 28 Vassileva P, Galabov AS. Combined therapy of epidemic keratoconjunctivitis. In: Bialasiewicz A. (ed.) Update of infectious diseases of the eye. New York: Springer Verlag; 1993: 307-314
    Google Scholar
  • 29 Galabov BS, Lozanova HS, Galabov AS. Method for obtaining of N’N’anhydrobis (β-hydroxyethyl) biguanide hydrochloride. Bulgarian Iinvention Certificate No. 41554, reg. No 74436/8.04.1986; transformed in Patent No 341/24.02.1994.
    PubMed
  • 30 Reed LJ, Muench H. A simple method of estimating fifty per cent endpoints. Am J Hyg 1938; 27: 493-497
    PubMedGoogle Scholar
  • 31 Millonig G. Advantages of a phosphate buffer for OsO4 solutions in fixation. J. Appl Phys 1961; 32: 1637
    PubMedGoogle Scholar
  • 32 Reynolds ES. The use of lead citrate at a high pH as an electron-opaque strain in electron microscopy. J Cell Biol 1963; 17: 208-212
    CrossrefPubMedGoogle Scholar
  • 33 Ghebremedhin B. Human adenovirus: Viral pathogen with increasing importance. Eur J. Microbiol Immunol (Bp) 2014; 4: 26-33
    PubMedGoogle Scholar
  • 34 Rosen L. A hemagglutination-inhibition technique for typing adenoviruses. Amer J Hyg 1960; 71: 120-128
    PubMedGoogle Scholar
  • 35 Norrby E, Wadell C. Soluble components of adenovirus type 4. Virology 1967; 31: 592-600
    CrossrefPubMedGoogle Scholar
  • 36 Morgan C, Godman GC, Rose HM. et al. Electron microscopic and histochemical studies of an usual crystalline protein occurring in cells infected by type 5 adenovirus. Preliminary observation. J Biophys Biochem Cytol 1957; 3: 505-508
    CrossrefPubMedGoogle Scholar
  • 37 Morgan C, Godman GD, Breittenfeld PM. et al. A correlative study by electron and light microscopy of the development of type 5 adenovirus. I. Electron microscopy. J Exp Med 1960; 112: 373-381
    CrossrefPubMedGoogle Scholar
  • 38 Martinez-Palomo A, Le Bois J, Bernhard W. Electron microscopy of adenovirus 12 replication.1. Fine structural changes in the nucleus in infected KB cells. J Virol 1967; 1: 817-829
    CrossrefPubMedGoogle Scholar
  • 39 Franqueville L, Henning P, Magnusson M. et al. Protein crystals in adenovirus type 5-infected cells : requirements for intranuclearcrystallogenesis, structural and functionalanalysis. PLoS One 2008; DOI: dx.doi.org/10.1371/jounal.pone.0002894.
    PubMedGoogle Scholar
  • 40 Torpier G, Petitprez A. Étude ultrastructurals de paracrystaux protéiques intranucléaires induits par adénovirus 5. Journ Microscopie 1968; 7: 411
    PubMedGoogle Scholar
  • 41 Weber J, Stich HF. Electron microscopy of cells infected with adenovirus type 2. J Virol 1969; 3: 198-204
    CrossrefPubMedGoogle Scholar
  • 42 Boulanger PA, Torpier G, Biserte G. Investigation on intranuclear paracrystalline inclusions induced by adenoviruys 5 in KB cells. J gen Virol 1971; 6: 329-332
    PubMedGoogle Scholar
  • 43 Boulanger PA, Puvion F. Large-scale preparation of soluble adenovirus hexon, penton and fiber antigens in highly purified form. Eur J Biochem 1973; 39: 37-42
    CrossrefPubMedGoogle Scholar
  • 44 Wills EJ, Russel WC, Williams JF. Adenovirus-induced crystals: studies with temperature-sensitive mutants. J gen Virol 1973; 20: 407-412
    CrossrefPubMedGoogle Scholar
  • 45 Henry CJ, Atchison RW. Paracrystal formation in cell cultures infected with adenovirus type 2. J Virol 1971; 8: 842-849
    CrossrefPubMedGoogle Scholar
  • 46 Henry CJ, Slifkin M, Merkow LP. et al. The ultrastructure and nature of adenovirus type 2-induced paracrystalline formation. Virol 1971; 44: 215-218
    CrossrefPubMedGoogle Scholar
  • 47 Marusyk R, Norby E, Marusyk H. The relationship of adenovirus-induced paracrystalline structures to the virus core protein(s). J gen Virol 1972; 14: 261-270
    CrossrefPubMedGoogle Scholar
  • 48 Carstens EB, Marusyk RG. Crystallization and reaggregation of adenovirus type 5 structural components from infected cell extracts. J gen Virol 1977; 34: 541-545
    CrossrefPubMedGoogle Scholar
  • 49 Weber J. Physical mapping of the genes controlling adenovirus paracrystal formation. Canadian J Microbiol 1978; 24: 1381-1386
    CrossrefPubMedGoogle Scholar
  • 50 Wodrich H, Guan T, Cingolani G. et al. Switch from capsid protein import to adenovirus assembly by cleavage of nuclear transport signals. EMBO J 2003; 22: 6245-6255
    CrossrefPubMedGoogle Scholar