A Common Mode of Antiviral Action for Ammonium Ions and Various Amines

Fletcher, Ronald D.; Hirschfield, J. E.; Forbes, M.

doi:10.1038/207664a0

Cited by 25 publications

(21 citation statements)

References 9 publications

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“…The effect of ammonium ions on influenza virus infection was described independently by Jensen et al (1961) and Eaton & Scala (1961), and was later extended to a large number of aliphatic amines (Jensen & Liu, 1963;Fletcher et al, 1965). The inhibitory effect of chloroquine has been reported with myxoviruses (Inglot, 1969;Schimizu et al, 1972;Matlin et al, 1981), rhabdoviruses (Schimizu et al, 1972;, retroviruses (Pazmino et al, 1974), togaviruses (Inglot, 1969, Helenius et al, 1980aTalbot & Vance, 1980), paramyxoviruses (Inglot, 1969;Schimizu et al, 1972;Durand et al, 1970), herpes viruses (Lancz et al, 1971;Banfield & Kirsch, 1973) and mouse hepatitis virus (Malucci, 1966).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Semliki Forest Virus Penetration by Lysosomotropic Weak Bases

Helenius

Marsh

White

1982

Journal of General Virology

240

157

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SUMMARYThe effect of five lysosomotropic weak bases (chloroquine, amantadine, tributylamine, methylamine and NH4CI) on Semliki Forest virus (SFV) infection has been studied in BHK-21 cells. When present at concentrations equal to or greater than 0-1, 0.5, 2, 15 and 15 mM respectively, the agents inhibited SFV infection by more than 90%. The effect was reversible and involved a process occurring within the first 60 min of virus-cell contact. The agents did not have a direct virucidal effect nor did they affect virus binding to the cells, receptor-mediated endocytosis of prebound virus, intracellular distribution of virus after endocytosis, or the low pH-induced membrane fusion activity of the virus spike glycoproteins. The step blocked by chloroquine and NH4CI occurred intracellularly and was identified as the release of the virus nucleocapsid into the cytoplasm or the uncoating process. On the basis of these results, our previous studies on SFV entry, and the known effects of lipophilic amines on lysosomes, we conclude that the agents affect entry by a common mechanism: they prevent the transfer of the virus nucleocapsid into the cytoplasm by increasing the lysosomal pH above the critical value needed to trigger a low pH-dependent fusion reaction between the membranes of the tysosome and the virus.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Semliki Forest Virus Penetration by Lysosomotropic Weak Bases

Helenius

Marsh

White

1982

Journal of General Virology

240

157

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“…The evidence of fusion activity at around pH 5.5 has been presented above but evidence that particles fuse with the membrane of lysosomal vesicles is not available at present. However, the multiplication of influenza viruses is inhibited by NH4OH (Eaton & Scala, 1961), NH4C1 (Fletcher et al, 1965;t~iampor & Kr~anovh, 1971) and amantadine, lysosomotropic agents which raise intracellular pH (Ohkuma & Poole, 1978) and several studies indicate that amantadine interferes with a stage shortly after attachment and before any virus-directed synthesis can be detected (Hoffman et al, 1965;Kato & Eggers, 1969;Koff & Knight, 1979;Long & Olusanya, 1972;Skehel et al, 1977). Evidence that influenza viruses are uncoated at 4 °C, with virus RNP in the nucleus and envelope in the cytoplasm (Kato & Eggers, 1969;Stephenson & Dimmock, 1975;Hudson et al, 1978;Possee & Dimmock, 1981), suggests either that uncoating by fusion takes place at an unusually low temperature or that the virus uncoats by some mechanism about which we know nothing.…”

Section: Fusion Of Enveloped Virus With the Vesicle Membranementioning

confidence: 99%

Initial Stages in Infection with Animal Viruses

Dimmock

1982

Journal of General Virology

171

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“…[5][6][7][8][9][10] The major mode of cell death after treatment with DNA damaging agents is apoptosis. 21,22 It was reported that many adamantane compounds are potent inducers of apoptosis in a variety of malignant cell types in vitro and in vivo, including solid tumors and various leukemias.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7][8][9][10] It was proposed that the most fascinating tasks for cancer researchers would be the investigation of adamantane compounds as potential antiviral and antitumor agents. For this reason, apoptosis, as an important phenomenon of cell death in cancer chemotherapy, was analyzed.…”

Section: Introductionmentioning

confidence: 99%

Radioprotective and Antitumor Activity Evaluation of Newly Synthesized Adamantyl Tenocyclidines

Ferle-Vidović

Jukić

Škare

et al. 2003

Cancer Biotherapy and Radiopharmaceuticals

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Several adamantyl derivatives of thienyl phencyclidine (tenocyclidine; TCP) were newly sythesized and characterized: adamantyl derivatives containing piperidine (TAPIP), pyrrolidine (TAPYR), and morpholine (TAMORPH) groups. Their biological activity was evaluated by in vitro testing of their effect on the proliferative and reproductive ability (cytotoxicity) of a human tumor cell strain and nonmalignant mouse fibroblasts in culture. We also tested them for their radioprotective effect after ionizing irradiation, and as anticancer agents on the same human tumor cell strain. Compared with TCP, adamantyl derivatives are less toxic and have outstanding radioprotective properties. These derivatives (especially TAMORPH) increase apoptotic death of human malignant cells. The radiation-modifying effect studied on C3Hf mice in vivo showed that the adamantyl derivatives of TCP have a more enhanced radioprotective effect and that they are less toxic than TCP itself. The present data are discussed and compared with those previously reported for structurally related phencyclidine derivatives.

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A Common Mode of Antiviral Action for Ammonium Ions and Various Amines

Cited by 25 publications

References 9 publications

Inhibition of Semliki Forest Virus Penetration by Lysosomotropic Weak Bases

Inhibition of Semliki Forest Virus Penetration by Lysosomotropic Weak Bases

Initial Stages in Infection with Animal Viruses

Radioprotective and Antitumor Activity Evaluation of Newly Synthesized Adamantyl Tenocyclidines

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