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Abstract:

Several arenaviruses can cause severe hemorrhagic fever (HF) in humans, representing a public health threat in endemic areas of Africa and South America. The present study characterizes the potent virucidal activity of the carboxamide-derivatized aromatic disulfide NSC4492, an antiretroviral zinc finger-reactive compound, against Junín virus (JUNV), the causative agent of Argentine HF. The compound was able to inactivate JUNV in a time and temperature-dependent manner, producing more than 99% reduction in virus titer upon incubation with virions at 37° C for 90 min. The ability of NSC4492-treated JUNV to go through different steps of the multiplication cycle was then evaluated. Inactivated virions were able to bind and enter into the host cell with similar efficiency as control infectious particles. In contrast, treatment with NSC4492 impaired the capacity of JUNV to drive viral RNA synthesis, as measured by quantitative RT-PCR, and blocked viral protein expression, as determined by indirect immunofluorescence. These results suggest that the disulfide NSC4492 targets on the arenavirus replication complex leading to impairment in viral RNA synthesis. Additionally, analysis of VLP produced in NSC4492-treated cells expressing JUNV matrix Z protein revealed that the compound may interact with Z resulting in an altered aggregation behavior of this protein, but without affecting its intrinsic self-budding properties. The potential perspectives of NSC4492 as an inactivating vaccinal compound for pathogenic arenaviruses are discussed. © 2013 Sepúlveda et al.

Registro:

Documento: Artículo
Título:Targeting of arenavirus RNA synthesis by a carboxamide-derivatized aromatic disulfide with virucidal activity
Autor:Sepúlveda, C.S.; García, C.C.; Levingston Macleod, J.M.; López, N.; Damonte, E.B.
Filiación:Departamento de Química Biológica, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Centro de Virología Animal (CEVAN), Instituto de Ciencia Y Tecnología Dr. César Milstein, CONICET, Buenos Aires, Argentina
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
Palabras clave:antivirus agent; disulfide; hydrazine derivative; NSC4492; virus RNA; animal; Arenavirus; cell line; Chlorocebus aethiops; dose response; drug effects; genetic transcription; genetics; human; physiology; temperature; Vero cell line; virus release; virus replication; Animals; Antiviral Agents; Arenavirus; Cell Line; Cercopithecus aethiops; Disulfides; Dose-Response Relationship, Drug; Humans; Hydrazines; RNA, Viral; Temperature; Transcription, Genetic; Vero Cells; Virus Release; Virus Replication
Año:2013
Volumen:8
Número:11
DOI: http://dx.doi.org/10.1371/journal.pone.0081251
Título revista:PLoS ONE
Título revista abreviado:PLoS ONE
ISSN:19326203
CODEN:POLNC
CAS:disulfide, 16734-12-6; Antiviral Agents; Disulfides; Hydrazines; NSC4492; RNA, Viral
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v8_n11_p_Sepulveda

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Citas:

---------- APA ----------
Sepúlveda, C.S., García, C.C., Levingston Macleod, J.M., López, N. & Damonte, E.B. (2013) . Targeting of arenavirus RNA synthesis by a carboxamide-derivatized aromatic disulfide with virucidal activity. PLoS ONE, 8(11).
http://dx.doi.org/10.1371/journal.pone.0081251
---------- CHICAGO ----------
Sepúlveda, C.S., García, C.C., Levingston Macleod, J.M., López, N., Damonte, E.B. "Targeting of arenavirus RNA synthesis by a carboxamide-derivatized aromatic disulfide with virucidal activity" . PLoS ONE 8, no. 11 (2013).
http://dx.doi.org/10.1371/journal.pone.0081251
---------- MLA ----------
Sepúlveda, C.S., García, C.C., Levingston Macleod, J.M., López, N., Damonte, E.B. "Targeting of arenavirus RNA synthesis by a carboxamide-derivatized aromatic disulfide with virucidal activity" . PLoS ONE, vol. 8, no. 11, 2013.
http://dx.doi.org/10.1371/journal.pone.0081251
---------- VANCOUVER ----------
Sepúlveda, C.S., García, C.C., Levingston Macleod, J.M., López, N., Damonte, E.B. Targeting of arenavirus RNA synthesis by a carboxamide-derivatized aromatic disulfide with virucidal activity. PLoS ONE. 2013;8(11).
http://dx.doi.org/10.1371/journal.pone.0081251