Inhibitory Effects of Atropine, Protamine, and Their Combination on Hepatitis A Virus Replication in PLC/PRF/5 Cells

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 1990 Jun 1

PMID 2168143

Citations 3

Authors

E Biziagos

J M Crance

J Passagot

R Deloince

Affiliations

Soon will be listed here.

Abstract

Atropine, protamine, and the combination of these drugs were tested for their effects on hepatitis A virus (HAV) replication in cell culture. PLC/PRF/5 hepatoma cells were treated simultaneously with nontoxic concentrations of these drugs and inoculated with HAV strain CF 53 at several multiplicities of infection. The yields of infectious HAV after 4 and 15 days were markedly reduced by each drug, especially at the lowest multiplicity of infection. The activities of each drug were irreversible. Atropine was active when it was added as late as 2 h after inoculation with HAV. An anti-HAV effect was also induced by treating cells with atropine prior to inoculation. Protamine was active as late as 6 h postinoculation. The combination of atropine and protamine resulted in an enhanced anti-HAV effect. We concluded that these drugs affect undetermined, but separate, steps in the HAV replication cycle.

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References

JAQUES L . Protamine--antagonist to heparin. Can Med Assoc J. 1973; 108(10):1291-7. PMC: 1941450. View

BERENBAUM M . A method for testing for synergy with any number of agents. J Infect Dis. 1978; 137(2):122-30. DOI: 10.1093/infdis/137.2.122. View

Ayisi N, Gupta V, Meldrum J, Taneja A, Babiuk L . Combination chemotherapy: interaction of 5-methoxymethyldeoxyuridine with adenine arabinoside, 5-ethyldeoxyuridine, 5-iododeoxyuridine, and phosphonoacetic acid against herpes simplex virus types 1 and 2. Antimicrob Agents Chemother. 1980; 17(4):558-66. PMC: 283832. DOI: 10.1128/AAC.17.4.558. View

Hayden F, DOUGLAS Jr R, Simons R . Enhancement of activity against influenza viruses by combinations of antiviral agents. Antimicrob Agents Chemother. 1980; 18(4):536-41. PMC: 284045. DOI: 10.1128/AAC.18.4.536. View

YAMAZAKI Z, TAGAYA I . Antiviral effects of atropine and caffeine. J Gen Virol. 1980; 50(2):429-31. DOI: 10.1099/0022-1317-50-2-429. View

Talib S, Banerjee A . Protamine--a potent inhibitor of vesicular stomatitis virus transcriptase in vitro. Biochem Biophys Res Commun. 1981; 98(3):875-83. DOI: 10.1016/0006-291x(81)91192-x. View

Siegl G, Eggers H . Failure of guanidine and 2-(alpha-hydroxybenzyl)benzimidazole to inhibit replication of hepatitis A virus in vitro. J Gen Virol. 1982; 61 (Pt l):111-4. DOI: 10.1099/0022-1317-61-1-111. View

Schinazi R, Peters J, Williams C, Chance D, Nahmias A . Effect of combinations of acyclovir with vidarabine or its 5'-monophosphate on herpes simplex viruses in cell culture and in mice. Antimicrob Agents Chemother. 1982; 22(3):499-507. PMC: 183772. DOI: 10.1128/AAC.22.3.499. View

Allen L, Vanderslice L, Fingal C, McCright F, HARRIS E, Cook P . Evaluation of the anti-herpesvirus drug combinations: virazole plus arabinofuranosylhypoxanthine and virazole plus arabinofuranosyladenine. Antiviral Res. 1982; 2(4):203-16. DOI: 10.1016/0166-3542(82)90043-2. View

10.

Widell A, Hansson B, Moestrup T, Serleus Z, Mathiesen L, JOHNSSON T . Acute hepatitis A, B and non-A, non-B in a Swedish community studied over a ten-year period. Scand J Infect Dis. 1982; 14(4):253-9. DOI: 10.3109/inf.1982.14.issue-4.02. View

11.

Alarcon B, Gonzalez M, Carrasco L . Antiherpesvirus action of atropine. Antimicrob Agents Chemother. 1984; 26(5):702-6. PMC: 179999. DOI: 10.1128/AAC.26.5.702. View

12.

Lemon S . Type A viral hepatitis. New developments in an old disease. N Engl J Med. 1985; 313(17):1059-67. DOI: 10.1056/NEJM198510243131706. View

13.

Crance J, Passagot J, Verwaerde N, Biziagos E, Gandre H, Deloince R . [Adaptation to the cell line PLC/PRF/5 of hepatitis A virus released in the cell culture medium]. C R Acad Sci III. 1985; 301(7):361-3. View

14.

Wheeler C, Fields H, Schable C, Meinke W, MAYNARD J . Adsorption, purification, and growth characteristics of hepatitis A virus strain HAS-15 propagated in fetal rhesus monkey kidney cells. J Clin Microbiol. 1986; 23(3):434-40. PMC: 268669. DOI: 10.1128/jcm.23.3.434-440.1986. View

15.

Widell A, Hansson B, Oberg B, Nordenfelt E . Influence of twenty potentially antiviral substances on in vitro multiplication of hepatitis A virus. Antiviral Res. 1986; 6(2):103-12. DOI: 10.1016/0166-3542(86)90030-6. View

16.

Smith T, Kremer M, Luo M, Vriend G, Arnold E, Kamer G . The site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating. Science. 1986; 233(4770):1286-93. DOI: 10.1126/science.3018924. View

17.

Gaffey M, Gwaltney Jr J, Dressler W, Sorrentino J, Hayden F . Intranasally administered atropine methonitrate treatment of experimental rhinovirus colds. Am Rev Respir Dis. 1987; 135(1):241-4. DOI: 10.1164/arrd.1987.135.1.241. View

18.

Biziagos E, Crance J, Passagot J, Deloince R . Effect of antiviral substances on hepatitis A virus replication in vitro. J Med Virol. 1987; 22(1):57-66. DOI: 10.1002/jmv.1890220108. View

19.

Superti F, Seganti L, Orsi N, Divizia M, Gabrieli R, Pana A . The effect of lipophilic amines on the growth of hepatitis A virus in Frp/3 cells. Arch Virol. 1987; 96(3-4):289-96. DOI: 10.1007/BF01320970. View

20.

Crance J, Passagot J, Biziagos E, Deloince R . Continuous production of hepatitis A virus in PLC/PRF/5 cell cultures: use of antigen for serology. J Virol Methods. 1987; 18(2-3):193-203. DOI: 10.1016/0166-0934(87)90124-8. View