Artículo

Sepúlveda, C.S.; García, C.C.; Fascio, M.L.; D'Accorso, N.B.; Docampo Palacios, M.L.; Pellón, R.F.; Damonte, E.B. "Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative" (2012) Antiviral Research. 93(1):16-22
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Abstract:

There are no specific approved drugs for the treatment of agents of viral hemorrhagic fevers (HF) and antiviral therapies against these viruses are urgently needed. The present study characterizes the potent and selective antiviral activity against the HF causing arenavirus Junin virus (JUNV) of the compound 10-allyl-6-chloro-4-methoxy-9(10H)-acridone, designated 3f. The effectiveness of 3f to inhibit JUNV multiplication was not importantly affected by the initial multiplicity of infection, with similar effective concentration 50% (EC 50) values in virus yield inhibition assays performed in Vero cells in the range of 0.2-40 plaque forming units (PFU)/cell. Mechanistic studies demonstrated that 3f did not affect the initial steps of adsorption and internalization. The subsequent process of viral RNA synthesis was strongly inhibited, as quantified by real time RT-PCR in compound-treated cells relative to non-treated cells. The addition of exogenous guanosine rescued the infectivity and RNA synthesis of JUNV in 3f-treated cells in a dose-dependent manner, but the reversal was partial, suggesting that the reduction of the GTP pool contributed to the antiviral activity of 3f, but it was not the main operative mechanism. The comparison of 3f with two other viral RNA inhibitors, ribavirin and mycophenolic acid, showed that ribavirin did not act against JUNV through the cellular enzyme inosine monophosphate dehydrogenase (IMPDH) inhibition whereas the anti-JUNV activity of mycophenolic acid was mainly targeted at this enzyme. © 2011 Elsevier B.V.

Registro:

Documento: Artículo
Título:Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative
Autor:Sepúlveda, C.S.; García, C.C.; Fascio, M.L.; D'Accorso, N.B.; Docampo Palacios, M.L.; Pellón, R.F.; Damonte, E.B.
Filiación:Laboratorio de Virología, Departamento de Química Biológica Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Piso 4, 1428 Buenos Aires, Argentina
CIHIDECAR (CONICET), Departamento de Química Orgánica Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires Ciudad Universitaria, Pabellón 2, Piso 3, 1428 Buenos Aires, Argentina
Palabras clave:Acridone; Antiviral; Hemorrhagic fever virus; Inosine monophosphate dehydrogenase (IMPDH); Junin virus; RNA synthesis; 10 allyl 6 chloro 4 methoxy 9(10h)acridone; acridone derivative; guanosine; inosinate dehydrogenase; mycophenolic acid; ribavirin; unclassified drug; virus RNA; adsorption; animal cell; antiviral activity; article; controlled study; drug potency; hemorrhagic fever; infection; internalization; Junin virus; nonhuman; priority journal; real time polymerase chain reaction; RNA synthesis; Vero cell; virogenesis; Acridones; Allyl Compounds; Animals; Antiviral Agents; Cercopithecus aethiops; Cytopathogenic Effect, Viral; Gene Expression Regulation, Viral; Guanosine; Junin virus; Microbial Sensitivity Tests; RNA, Viral; Vero Cells; Virus Replication; Arenavirus; Junin virus
Año:2012
Volumen:93
Número:1
Página de inicio:16
Página de fin:22
DOI: http://dx.doi.org/10.1016/j.antiviral.2011.10.007
Título revista:Antiviral Research
Título revista abreviado:Antiviral Res.
ISSN:01663542
CODEN:ARSRD
CAS:guanosine, 118-00-3; inosinate dehydrogenase, 9028-93-7; mycophenolic acid, 23047-11-2, 24280-93-1; ribavirin, 36791-04-5; 10-allyl-6-chloro-4-methoxy-9(10H)-acridone; Acridones; Allyl Compounds; Antiviral Agents; Guanosine, 118-00-3; RNA, Viral
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01663542_v93_n1_p16_Sepulveda

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Citas:

---------- APA ----------
Sepúlveda, C.S., García, C.C., Fascio, M.L., D'Accorso, N.B., Docampo Palacios, M.L., Pellón, R.F. & Damonte, E.B. (2012) . Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative. Antiviral Research, 93(1), 16-22.
http://dx.doi.org/10.1016/j.antiviral.2011.10.007
---------- CHICAGO ----------
Sepúlveda, C.S., García, C.C., Fascio, M.L., D'Accorso, N.B., Docampo Palacios, M.L., Pellón, R.F., et al. "Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative" . Antiviral Research 93, no. 1 (2012) : 16-22.
http://dx.doi.org/10.1016/j.antiviral.2011.10.007
---------- MLA ----------
Sepúlveda, C.S., García, C.C., Fascio, M.L., D'Accorso, N.B., Docampo Palacios, M.L., Pellón, R.F., et al. "Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative" . Antiviral Research, vol. 93, no. 1, 2012, pp. 16-22.
http://dx.doi.org/10.1016/j.antiviral.2011.10.007
---------- VANCOUVER ----------
Sepúlveda, C.S., García, C.C., Fascio, M.L., D'Accorso, N.B., Docampo Palacios, M.L., Pellón, R.F., et al. Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative. Antiviral Res. 2012;93(1):16-22.
http://dx.doi.org/10.1016/j.antiviral.2011.10.007