Targeting of arenavirus RNA synthesis by a carboxamide-derivatized aromatic disulfide with virucidal activity

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 fi...

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Autores principales:	Sepúlveda, Claudia Soledad, García, Cybele Carina, López, Nora Mabel, Damonte, Elsa Beatriz
Publicado:	2013
Materias:	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 Cell Line Cercopithecus aethiops Disulfides Dose-Response Relationship, Drug Humans Hydrazines RNA, Viral Temperature Transcription, Genetic Vero Cells Virus Release Virus Replication
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v8_n11_p_Sepulveda http://hdl.handle.net/20.500.12110/paper_19326203_v8_n11_p_Sepulveda
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_19326203_v8_n11_p_Sepulveda
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spelling	paper:paper_19326203_v8_n11_p_Sepulveda2023-06-08T16:31:12Z Targeting of arenavirus RNA synthesis by a carboxamide-derivatized aromatic disulfide with virucidal activity Sepúlveda, Claudia Soledad García, Cybele Carina López, Nora Mabel Damonte, Elsa Beatriz 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 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. Fil:Sepúlveda, C.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:García, C.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:López, N. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Damonte, E.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2013 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v8_n11_p_Sepulveda http://hdl.handle.net/20.500.12110/paper_19326203_v8_n11_p_Sepulveda
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Sepúlveda, Claudia Soledad García, Cybele Carina López, Nora Mabel Damonte, Elsa Beatriz Targeting of arenavirus RNA synthesis by a carboxamide-derivatized aromatic disulfide with virucidal activity
topic_facet	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
description	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.
author	Sepúlveda, Claudia Soledad García, Cybele Carina López, Nora Mabel Damonte, Elsa Beatriz
author_facet	Sepúlveda, Claudia Soledad García, Cybele Carina López, Nora Mabel Damonte, Elsa Beatriz
author_sort	Sepúlveda, Claudia Soledad
title	Targeting of arenavirus RNA synthesis by a carboxamide-derivatized aromatic disulfide with virucidal activity
title_short	Targeting of arenavirus RNA synthesis by a carboxamide-derivatized aromatic disulfide with virucidal activity
title_full	Targeting of arenavirus RNA synthesis by a carboxamide-derivatized aromatic disulfide with virucidal activity
title_fullStr	Targeting of arenavirus RNA synthesis by a carboxamide-derivatized aromatic disulfide with virucidal activity
title_full_unstemmed	Targeting of arenavirus RNA synthesis by a carboxamide-derivatized aromatic disulfide with virucidal activity
title_sort	targeting of arenavirus rna synthesis by a carboxamide-derivatized aromatic disulfide with virucidal activity
publishDate	2013
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v8_n11_p_Sepulveda http://hdl.handle.net/20.500.12110/paper_19326203_v8_n11_p_Sepulveda
work_keys_str_mv	AT sepulvedaclaudiasoledad targetingofarenavirusrnasynthesisbyacarboxamidederivatizedaromaticdisulfidewithvirucidalactivity AT garciacybelecarina targetingofarenavirusrnasynthesisbyacarboxamidederivatizedaromaticdisulfidewithvirucidalactivity AT lopeznoramabel targetingofarenavirusrnasynthesisbyacarboxamidederivatizedaromaticdisulfidewithvirucidalactivity AT damonteelsabeatriz targetingofarenavirusrnasynthesisbyacarboxamidederivatizedaromaticdisulfidewithvirucidalactivity
_version_	1768545668310237184

Targeting of arenavirus RNA synthesis by a carboxamide-derivatized aromatic disulfide with virucidal activity

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