Skip to main content
SpringerLink
Log in
Book cover

Antiviral Drug Development pp 139–148Cite as

Assay Systems: Testing of Antiviral Drugs in Cell Culture (In Vitro)

  • Conference paper

Part of the book series: NATO ASI Series ((NSSA,volume 143))

Abstract

Testing for virus-inhibitory activity of chemicals in cell culture has sometimes furnished important leads in the development of antiviral drugs. The shortcomings of this so-called in vitro testing are obvious: substances which lack an effect on the viral replication cycle but, e.g., enhance antibody formation, improve nonspecific resistance, strengthen the interferon systems will not be detected by this method. Likewise, although so far only rarely described, some compounds affecting the viral replication cycle might reveal their antiviral effects only in an animal model, since metabolic activities of the organism, absent in cell culture, are required to convert the drug into its effective form. Most of the time, however, the reverse is true, viz. more compounds do appear active in a cell culture system than will later be found useful in the organism (Buthala, 1965; Eggers, 1977b). I shall refer to this problem in a later section.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aboud, M., and Hassan, Y., 1983, Accumulation and breakdown of RNA-deficient intracellular virus particles in interferon-treated NIH 3T3 cells chronically producing Moloney murine leukemia virus. J. Virol. 45:489–495.

    PubMed  CAS  Google Scholar 

  • Bablanian, R., Eggers, H.J., and Tamm, I., 1965, Studies on the mechanism of poliovirus-induced cell damage. I. The relation between poliovirus-induced metabolic and morphological alterations in cultured cells. Virology 26:100–113.

    Article  PubMed  CAS  Google Scholar 

  • Bauer, D.J., and Sadler, P.W., 1960, The structure-activity relationships of the antiviral chemotherapeutic activity of isatin β-thiosemicarbazone. Br. J. Pharmac. Chemother. 15:101–110.

    CAS  Google Scholar 

  • Bucknall, R.A., 1973, The continuing search for antiviral drugs Adv. Pharmacol. Chemotherapy 11:295–319.

    CAS  Google Scholar 

  • Buthala, D.A., 1965, Experience gained in screening for synthetic antiviral compounds. Ann. N.Y. Acad. Sci. 130:Art. 1, 17–23.

    Google Scholar 

  • Crowther, D., and Melnick, J.L., 1961, Studies of the inhibitory action of guanidine on poliovirus multiplication in cell cultures. Virology 15:65–74

    Article  PubMed  CAS  Google Scholar 

  • Davies, W.L., Grunert, R.R., Haff, R.F., McGahen, J.W., Neumayer, E.M., Paulshock, M., Watts, J.C., Wood, T.R., Herrmann, E.C., and Hoffmann, C.E., 1964, Antiviral activity of 1-adamantanamine (amantadine). Science 144:862–863.

    Article  PubMed  CAS  Google Scholar 

  • De Clercq, E., 1979, Suramin: a potent inhibitor of the reverse transcriptase of RNA tumor viruses Cancer Letters 8:9–22.

    Article  PubMed  Google Scholar 

  • De Clercq, E., Descamps, J., Verhelst, G., Walker, R.T., Jones, A.S., Torrence, P.F., and Shugar, D., 1980, Comparative efficacy of antiherpes drugs against different strains of herpes simplex virus. J. Inf. Dis. 141:563–574.

    Article  Google Scholar 

  • De Somer, P., and Prinzie, A., 1957, Poliomyelitis virus neutralizing antibodies determination by filter paper discs on solidified bottle cultures. Virology 4: 387–388.

    Article  Google Scholar 

  • Dulbecco, R., 1952, Production of plaques in monolayer tissue cultures by single particles of an animal virus. Proc. Natl. Acad. Sci. 38:747–752.

    Article  PubMed  CAS  Google Scholar 

  • Eggers, H.J., 1977a, Selective inhibition of uncoating of echovirus 12 by rhodanine. Virology 78:241–252.

    Article  PubMed  CAS  Google Scholar 

  • Eggers, H.J., 1977b, Specific antiviral substances: testing in experimental animals and in “in vitro” systems. In: International Symposium on Experimental Animals and “in vitro” Systems in Medical Microbiology. WHO Collaborating Centre for Collection and Evaluation of Data on Comparative Virology. Munich, pp. 277–282.

    Google Scholar 

  • Eggers, H.J., 1982, Benzimidazoles. Selective inhibitors of picornavirus replication in cell culture and in the organism. In: Chemotherapy of Viral Infections. P.E. Came, and L.A. Caliguiri (eds.) . Springer-Verlag Berlin, Heidelberg, New York, pp. 377–417.

    Chapter  Google Scholar 

  • Eggers, H.J., and Tamm, I., 1961, Spectrum and characteristics of the virus inhibitory action of 2-(α- hydroxybenzyl)-benzimidazole. J. Exp. Med. 113:657–682.

    Article  PubMed  CAS  Google Scholar 

  • Eggers, H.J., and Tamm, I., 1962, On the mechanism of selective inhibition of enterovirus multiplication by 2-(α-hydroxybenzyl)-benzimidazole. Virology 18:426–438.

    Article  CAS  Google Scholar 

  • Finter, N.B., 1970, Methods for screening in vitro and in vivo for agents active against myxoviruses. Ann. N.Y. Acad. Sci. 173:Art. 1, 131–138.

    Article  CAS  Google Scholar 

  • Gallo, R.C., Smith, R.C., Whang-Peng, J., Ting, R.C., Yang, S.S., and Abrell, J.W., 1972, RNA tumor viruses, DNA polymerases, and oncogenesis: some selective effects of rifampicin derivatives. Medicine 51:159–168.

    Article  PubMed  CAS  Google Scholar 

  • Griengl, H., Bodenteich, M., Hayden, W., Wanek, E., Streicher, W., Stütz, P., Bachmayer, H., Ghazzouli, I., and Rosenwirth, B., 1985, 5-(Haloalkyl)-2′-deoxyuridines: a novel type of potent antiviral nucleoside analogue. J.Med. Chem. 28:1679–1684.

    Article  PubMed  CAS  Google Scholar 

  • Hartmann, H., Hunsmann, G., and Eckstein, F., 1987, Inhibition of HIV-induced cytopathogeni ci ty in vitro by 3r-azi do-2′,3′-dideoxyguanosine. Lancet 1:115–116.

    Google Scholar 

  • Herrmann, E.C.,Jr., 1961, The detection, assay and evaluation of antiviral drugs. Progr. Med. Virol. 3:158–192.

    CAS  Google Scholar 

  • Herrmann, E.C.,Jr., Gabliks, J., Engle, C., and Perlman, P.L., 1960, Agar diffusion method for detection and bioassay of antiviral antibiotics. roc. Soc. Exp. Biol. Med. 103:625–628.

    CAS  Google Scholar 

  • Loddo, B., Ferrari, W., Brotzu, G., and Spanedda, A., 1962, In vitro inhibition of infectivity of polio viruses by guanidine. Nature 193:97–98.

    Article  PubMed  CAS  Google Scholar 

  • McCormick, J.B., King, I.J., Webb, P.A., Scribner, C.L., Craven, R.B., Johnson, K.M., Elliott, L.H., and Belmont-Williams, R., 1986, Lassa fever. Effective therapy with ribavirin. N. Engl. J. Med. 314:20–26.

    Article  PubMed  CAS  Google Scholar 

  • Meindl, P., Bodo, G., Palese, P., Schulman, J., and Tuppy, H., 1974, Inhibition of neuraminidase activity by derivatives of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. Virology 58:457–463.

    Article  PubMed  CAS  Google Scholar 

  • Miller, P.A., Lindsay, H.L., Cormier, M., Mayberry, B.R., and Trown, P.W., 1970, Rapid semi-automated procedures for assaying antiviral activity. Ann. N.Y. Acad. Sci. 173:Art. 1, 151–159.

    Article  CAS  Google Scholar 

  • Mitsuya, H., and Broder, S., 1986, Inhibition of the in vitro infectivity and cytopathic effect of human T-lymphotrophic virus type III/lymphadenopathy-associated virus (HTLV-III/ LAV) by 2′,3′-di deoxynucl eosides. Proc. Natl. Acad. Sci. 83:1911–1915.

    Article  PubMed  CAS  Google Scholar 

  • Palese, P., and Schulman, J.L., 1974, Inhibition of influenza and parainfluenza virus replication in tissue culture by 2-deoxy-2,3-dehydro-N-trifluoroacetylneuraminic acid (FANA). Virology 59:490–498.

    Article  PubMed  CAS  Google Scholar 

  • Pauwels, R., De Clercq, E., Desmyter, J., Balzarini, J., Goubau, P., Herdewijn, P., Vanderhaeghe, H., and Vandeputte, M., 1987, Sensitive and rapid assay on MT-4 cells for detection of antiviral compounds against the AIDS virus. J. Virol. Meth. in press.

    Google Scholar 

  • Rada, B, Blaškovič, D., Šorm, F., and Škoda, J., 1960, The inhibitory effect of 6-azauracil riboside on the multiplication of vaccinia virus. Experientia 15:487–488.

    Article  Google Scholar 

  • Rightsel, W.A., Dice, J.R., McAlpine, R.J., Timm, E.A., McLean, I.W., Jr., Dixon, G.J., and Schabel, F.M., Jr., 1961, Antiviral effect of guanidine. Science 134:558–559.

    Article  PubMed  CAS  Google Scholar 

  • Rightsel, W.A., Schultz, P., Muething, D., and McLean, I.W., Jr., 1956, Use of vinyl plastic containers in tissue cultures for virus assays. J. Immunol. 76:464–474.

    PubMed  CAS  Google Scholar 

  • Rosenwirth, B., and Eggers, H.J., 1977, Echovirus 12-induced host cell shutoff is prevented by rhodanine. Nature 267:370–371.

    Article  PubMed  CAS  Google Scholar 

  • Smith, R.A., and Canonico, P., 1984, Ribavirin. In: Anti­viral Drugs and Interferon: the Molecular Basis of their Activity, Y. Becker (ed.). Martinus Nijhoff Publishing, Boston, pp. 253–269.

    Chapter  Google Scholar 

  • Smith, Th.J., Kremer, M.J., Luo, M., Vriend, G., Arnold, E., Kamer, G., Rossmann, M.G., McKinlay, M.A., Diana, G.D., and Otto, M.J., 1986, The site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating. Science 233:1286–1293.

    Article  PubMed  CAS  Google Scholar 

  • Tamm, I., and Eggers, H.J., 1963, Unique susceptibility of enteroviruses to inhibition by 2-(03a1-hydroxybenzyl)-benzimidazole and derivatives. 2nd International Symposium of Chemotherapy, H.P. Kuemmerle, P. Preziosi, P. Rentchnick (eds.). S. Karger, Basel, New York, pp. 88–118.

    Google Scholar 

  • Tamm, I., Eggers, H.J., Bablanian, R., Wagner, A.F., and Folkers, K., 1969, Structural requirements of selective inhibition of enteroviruses by 2-(α-hydroxybenzyl)-benzimidazole and related compounds. Nature 223:785–788.

    Article  PubMed  CAS  Google Scholar 

  • Wendler, I., Bienzle, U., and Hunsmann, G., 1987, Neutralizing antibodies and the course of HIV induced disease. AIDS Research and Human Retroviruses, in press.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Virologie, Universität zu Köln, Fürst Pückler Str. 56, D-5000, Köln 41, Germany

    Hans J. Eggers

Authors
  1. Hans J. Eggers
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Katholieke Universiteit Leuven, Leuven, Belgium

    Erik De Clercq

  2. The University of Birmingham, Birmingham, UK

    Richard T. Walker

Rights and permissions

Reprints and permissions

Copyright information

© 1988 Plenum Press, New York

About this paper

Cite this paper

Eggers, H.J. (1988). Assay Systems: Testing of Antiviral Drugs in Cell Culture (In Vitro). In: De Clercq, E., Walker, R.T. (eds) Antiviral Drug Development. NATO ASI Series, vol 143. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-7275-2_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-7275-2_9

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-7277-6

  • Online ISBN: 978-1-4684-7275-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation