Abstract
The inhibition of herpesvirus type 1 in cell cultures by seven inhibitors of DNA synthesis and by pactamycin was investigated by plaque inhibition in Vero cells with agarose overlay, and by yield reduction in one-step growth in HeLa cells. While the plaque inhibition method proved to be suitable to show inhibition by single substances, only the yield reduction procedure was reliable for investigating the interaction of two substances. Inhibition was evaluated by means of an inhibition quotient (number of PFU in uninhibited virus controls∶number of PFU in test specimen); combined inhibition was related to results with single substances. Among the 28 substance pairs, 9 cases of indifference, 10 additive, and 9 synergistic interactions were found. Indifference was observed only with fluorodeoxyuridine and amethopterin as one of the partners, which by themselves inhibited herpesvirus multiplication incompletely.
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References
Acar JF (1978) Antibacterial synergy. Proceedings of a symposium. Introductory remarks. Infection, Supplement 1:5–8
Alford jr CA, Whitley RJ (1976) Treatment of infections due to herpesvirus in humans: A critical review of the state of the art. J Infect Dis 133 Suppl:A101–A108
Babiuk LA, Meldrum B, Gupta VS, Rouse BT (1975) Comparison of the antiviral effects of 5-methoxy-methyldeoxyuridine with 5-iododeoxyuridine, cytosine arabinoside, and adenine arabinoside. Antimicrob Agents Chemother 8:643–650
Baumunk CN, Friedman DL (1971) Absence of an effect of amethopterin and 5-fluorodeoxyuridine upon levels of thymidine triphosphate in HeLa cells. Canc Res 31:1930–1935
Bikbulatov RM, Grebenyuk VN (1977) The antiviral activity of combined 5-iodo-2-deoxyuridine and 6-aza-uridine experimentally and its effectiveness in treatment of herpetic infection involving the skin and mucous membranes. Vop Virus 21:228–231
Cheng Y-C, Goz B, Prusoff WH (1975) Deoxyribonucleotide metabolism in herpes simplex virus infected HeLa cells. Biochim Biophys Acta 390:253–263
Collins P, Bauer DJ (1977) Comparison of activity of herpes virus inhibitors. In: Chemotherapy of herpes simplex virus infections, Ed Oxford JS, Drasar FA, Williams JD. Academic Press London et al p 73–82
Fiala M, Chow AW, Miyasaki K, Guze LB (1974) Susceptibility of herpesvirus to three nucleoside analogues and their combinations and enhancement of the antiviral effect. J Infect Dis 129:82–85
Grytzmann B, Morr M, Wigand R (1980, in press) Derivatives of 3′- and 5′-deoxyadenosine: their inhibitory activity against DNA viruses. Chemotherapy
Hay J, Subak-Sharpe JH (1976) Mutants of herpes simplex virus types 1 and 2 that are resistant to phosphonoacetic acid induce altered DNA polymerase activities in infected cells. J gen Virol 31:145–148
Herrmann EC, Gabliks J, Engle C, Perlman PL (1960) Agar diffusion method for detection and bioassay of antiviral antibiotics. Proc Soc exper Biol Med 103:625–628
Jamieson AT, Bjursell G (1976) Deoxyribonucleoside triphosphate pools in herpes simplex type 1 infected cells. J gen Virol 31:101–113
Jawetz E (1968) Combined antibiotic action: Some definitions and correlations between laboratory and clinical results. Antimicrob Agents Chemother 1967:203–209
Kaufman HE (1965) In vivo studies with antiviral agents. Annals New York Acad Sci 130:168–180
Kaufman HE (1976) Ocular antiviral therapy in perspective. J Infect Dis 133 Suppl:A96–A100
Lerner AM, Bailey EJ (1974) Synergy of 9-β-D-arabino-furanosyladenine and human interferon against herpes simplex virus, type 1. J Infect Dis 130:549–552
Marks MI (1974) Variables influencing the in vitro susceptibilities of herpes simplex viruses to antiviral drugs. Antimicrob Agents Chemother 6:34–38
New York Academy of Sciences (1977) (Herrmann jr EC Ed) Third Conference of Antiviral Substances. Annals NY Acad Sci 284:1–720
Oxford JS, Drasar FA, Williams JD (Eds) (1977) Chemotherapy of herpes simplex virus infections. Academic Press London et al
Roy-Burman P (1970) Analogues of nucleic acid components. Recent Results in Cancer Research. Springer Berlin et al p 111
Shipkowitz NL, Bower RR, Appeli RN, Nordeen CW, Overby LR, Roderick WR, Schleicher JB, Von Esch AM (1973) Suppression of herpes simplex virus infection by phosphonoacetic acid. J Appl Microbiol 26:264–267
Whitley RJ, Soong S-J, Dolin R, Galasso GJ, Ch'ien LT, Alford CA and the Collaborative Study Group (1977) Adenine arabinoside therapy of biopsy-proved herpes simplex encephalitis. New Engl J Med 297:289–294
Wirjawan E, Wigand R (1978) Combined antiviral effect of DNA inhibitors on adenovirus multiplication. Chemotherapy 24:347–353
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Wigand, R., Hassinger, M. Combined antiviral effect of DNA inhibitors onHerpes simplex virus multiplication. Med Microbiol Immunol 168, 179–190 (1980). https://doi.org/10.1007/BF02122852
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DOI: https://doi.org/10.1007/BF02122852