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.
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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.
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.
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.
Bucknall, R.A., 1973, The continuing search for antiviral drugs Adv. Pharmacol. Chemotherapy 11:295–319.
Buthala, D.A., 1965, Experience gained in screening for synthetic antiviral compounds. Ann. N.Y. Acad. Sci. 130:Art. 1, 17–23.
Crowther, D., and Melnick, J.L., 1961, Studies of the inhibitory action of guanidine on poliovirus multiplication in cell cultures. Virology 15:65–74
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.
De Clercq, E., 1979, Suramin: a potent inhibitor of the reverse transcriptase of RNA tumor viruses Cancer Letters 8:9–22.
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.
De Somer, P., and Prinzie, A., 1957, Poliomyelitis virus neutralizing antibodies determination by filter paper discs on solidified bottle cultures. Virology 4: 387–388.
Dulbecco, R., 1952, Production of plaques in monolayer tissue cultures by single particles of an animal virus. Proc. Natl. Acad. Sci. 38:747–752.
Eggers, H.J., 1977a, Selective inhibition of uncoating of echovirus 12 by rhodanine. Virology 78:241–252.
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.
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.
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.
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.
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.
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.
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.
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.
Herrmann, E.C.,Jr., 1961, The detection, assay and evaluation of antiviral drugs. Progr. Med. Virol. 3:158–192.
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.
Loddo, B., Ferrari, W., Brotzu, G., and Spanedda, A., 1962, In vitro inhibition of infectivity of polio viruses by guanidine. Nature 193:97–98.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Rosenwirth, B., and Eggers, H.J., 1977, Echovirus 12-induced host cell shutoff is prevented by rhodanine. Nature 267:370–371.
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.
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.
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.
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.
Wendler, I., Bienzle, U., and Hunsmann, G., 1987, Neutralizing antibodies and the course of HIV induced disease. AIDS Research and Human Retroviruses, in press.
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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
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DOI: https://doi.org/10.1007/978-1-4684-7275-2_9
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