Arenavirus Z protein as an antiviral target: Virus inactivation and protein oligomerization by zinc finger-reactive compounds

Several disulfide-based and azoic compounds have shown antiviral and virucidal properties against arenaviruses in virus yield-inhibition and inactivation assays, respectively. The most effective virucidal agent, the aromatic disulfide NSC20625, was able to inactivate two strains of the prototype are...

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Autores principales:	García, C.C., Djavani, M., Topisirovic, I., Borden, K.L.B., Salvato, M.S., Damonte, E.B.
Formato:	JOUR
Materias:	1 (2 guanidine)phenyldisulfide 1,2 dithiane 4,5 diol 1,1 dioxide 3 nitrophenyldisulfide aldrithiol 2 antiinfective agent antivirus agent aromatic compound azoformamide bis[2 [n' (2,4 dichlorobenzal)]carboxamide 1 benzene]disulfide cysteine disulfide fatty acid binding protein metal ion nsc 203 nsc 20625 nsc 4493 nsc 624151 nsc 624152 promyelocytic leukemia protein recombinant protein ribavirin unclassified drug virus envelope protein virus glycoprotein virus protein virus RNA zinc finger protein antiviral activity Arenavirus article controlled study disulfide bond drug efficacy drug targeting electrophoresis human human cell Lymphocytic choriomeningitis virus molecular weight nonhuman oligomerization priority journal protein aggregation protein function protein motif RNA replication virion virus inactivation virus infection virus inhibition virus particle virus strain Animals Azo Compounds Carrier Proteins Cell Line Disulfides Humans Oligodeoxyribonucleotides RNA, Viral Virus Replication Zinc Fingers
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00221317_v87_n5_p1217_Garcia
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_00221317_v87_n5_p1217_Garcia2023-10-03T14:27:24Z Arenavirus Z protein as an antiviral target: Virus inactivation and protein oligomerization by zinc finger-reactive compounds García, C.C. Djavani, M. Topisirovic, I. Borden, K.L.B. Salvato, M.S. Damonte, E.B. 1 (2 guanidine)phenyldisulfide 1,2 dithiane 4,5 diol 1,1 dioxide 3 nitrophenyldisulfide aldrithiol 2 antiinfective agent antivirus agent aromatic compound azoformamide bis[2 [n' (2,4 dichlorobenzal)]carboxamide 1 benzene]disulfide cysteine disulfide fatty acid binding protein metal ion nsc 203 nsc 20625 nsc 4493 nsc 624151 nsc 624152 promyelocytic leukemia protein recombinant protein ribavirin unclassified drug virus envelope protein virus glycoprotein virus protein virus RNA zinc finger protein antiviral activity Arenavirus article controlled study disulfide bond drug efficacy drug targeting electrophoresis human human cell Lymphocytic choriomeningitis virus molecular weight nonhuman oligomerization priority journal protein aggregation protein function protein motif RNA replication virion virus inactivation virus infection virus inhibition virus particle virus strain Animals Azo Compounds Carrier Proteins Cell Line Disulfides Humans Lymphocytic choriomeningitis virus Oligodeoxyribonucleotides RNA, Viral Virus Replication Zinc Fingers Arenavirus Lymphocytic choriomeningitis virus Several disulfide-based and azoic compounds have shown antiviral and virucidal properties against arenaviruses in virus yield-inhibition and inactivation assays, respectively. The most effective virucidal agent, the aromatic disulfide NSC20625, was able to inactivate two strains of the prototype arenavirus species Lymphocytic choriomeningitis virus (LCMV). Inactivated viral particles retained the biological functions of the virion envelope glycoproteins in virus binding and uptake, but were unable to perform viral RNA replication. Furthermore, in inactivated virions, the electrophoretic profile of the Z protein was altered when analysed under non-reducing conditions, whereas the patterns of the proteins NP and GP1 remained unaffected. Treatment of a recombinant LCMV Z protein with the virucidal agents induced unfolding and oligomerization of Z to high-molecular-mass aggregates, probably due to metal-ion ejection and the formation of intermolecular disulfide bonds through the cysteine residues of the Z RING finger. NSC20625 also exhibited antiviral properties in LCMV-infected cells without affecting other cellular RING-motif proteins, such as the promyelocytic leukaemia protein PML. Altogether, the investigations described here illustrate the potential of the Z protein as a promising target for therapy and the prospects of the Z-reactive compounds to prevent arenavirus dissemination. © 2006 SGM. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00221317_v87_n5_p1217_Garcia
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	1 (2 guanidine)phenyldisulfide 1,2 dithiane 4,5 diol 1,1 dioxide 3 nitrophenyldisulfide aldrithiol 2 antiinfective agent antivirus agent aromatic compound azoformamide bis[2 [n' (2,4 dichlorobenzal)]carboxamide 1 benzene]disulfide cysteine disulfide fatty acid binding protein metal ion nsc 203 nsc 20625 nsc 4493 nsc 624151 nsc 624152 promyelocytic leukemia protein recombinant protein ribavirin unclassified drug virus envelope protein virus glycoprotein virus protein virus RNA zinc finger protein antiviral activity Arenavirus article controlled study disulfide bond drug efficacy drug targeting electrophoresis human human cell Lymphocytic choriomeningitis virus molecular weight nonhuman oligomerization priority journal protein aggregation protein function protein motif RNA replication virion virus inactivation virus infection virus inhibition virus particle virus strain Animals Azo Compounds Carrier Proteins Cell Line Disulfides Humans Lymphocytic choriomeningitis virus Oligodeoxyribonucleotides RNA, Viral Virus Replication Zinc Fingers Arenavirus Lymphocytic choriomeningitis virus
spellingShingle	1 (2 guanidine)phenyldisulfide 1,2 dithiane 4,5 diol 1,1 dioxide 3 nitrophenyldisulfide aldrithiol 2 antiinfective agent antivirus agent aromatic compound azoformamide bis[2 [n' (2,4 dichlorobenzal)]carboxamide 1 benzene]disulfide cysteine disulfide fatty acid binding protein metal ion nsc 203 nsc 20625 nsc 4493 nsc 624151 nsc 624152 promyelocytic leukemia protein recombinant protein ribavirin unclassified drug virus envelope protein virus glycoprotein virus protein virus RNA zinc finger protein antiviral activity Arenavirus article controlled study disulfide bond drug efficacy drug targeting electrophoresis human human cell Lymphocytic choriomeningitis virus molecular weight nonhuman oligomerization priority journal protein aggregation protein function protein motif RNA replication virion virus inactivation virus infection virus inhibition virus particle virus strain Animals Azo Compounds Carrier Proteins Cell Line Disulfides Humans Lymphocytic choriomeningitis virus Oligodeoxyribonucleotides RNA, Viral Virus Replication Zinc Fingers Arenavirus Lymphocytic choriomeningitis virus García, C.C. Djavani, M. Topisirovic, I. Borden, K.L.B. Salvato, M.S. Damonte, E.B. Arenavirus Z protein as an antiviral target: Virus inactivation and protein oligomerization by zinc finger-reactive compounds
topic_facet	1 (2 guanidine)phenyldisulfide 1,2 dithiane 4,5 diol 1,1 dioxide 3 nitrophenyldisulfide aldrithiol 2 antiinfective agent antivirus agent aromatic compound azoformamide bis[2 [n' (2,4 dichlorobenzal)]carboxamide 1 benzene]disulfide cysteine disulfide fatty acid binding protein metal ion nsc 203 nsc 20625 nsc 4493 nsc 624151 nsc 624152 promyelocytic leukemia protein recombinant protein ribavirin unclassified drug virus envelope protein virus glycoprotein virus protein virus RNA zinc finger protein antiviral activity Arenavirus article controlled study disulfide bond drug efficacy drug targeting electrophoresis human human cell Lymphocytic choriomeningitis virus molecular weight nonhuman oligomerization priority journal protein aggregation protein function protein motif RNA replication virion virus inactivation virus infection virus inhibition virus particle virus strain Animals Azo Compounds Carrier Proteins Cell Line Disulfides Humans Lymphocytic choriomeningitis virus Oligodeoxyribonucleotides RNA, Viral Virus Replication Zinc Fingers Arenavirus Lymphocytic choriomeningitis virus
description	Several disulfide-based and azoic compounds have shown antiviral and virucidal properties against arenaviruses in virus yield-inhibition and inactivation assays, respectively. The most effective virucidal agent, the aromatic disulfide NSC20625, was able to inactivate two strains of the prototype arenavirus species Lymphocytic choriomeningitis virus (LCMV). Inactivated viral particles retained the biological functions of the virion envelope glycoproteins in virus binding and uptake, but were unable to perform viral RNA replication. Furthermore, in inactivated virions, the electrophoretic profile of the Z protein was altered when analysed under non-reducing conditions, whereas the patterns of the proteins NP and GP1 remained unaffected. Treatment of a recombinant LCMV Z protein with the virucidal agents induced unfolding and oligomerization of Z to high-molecular-mass aggregates, probably due to metal-ion ejection and the formation of intermolecular disulfide bonds through the cysteine residues of the Z RING finger. NSC20625 also exhibited antiviral properties in LCMV-infected cells without affecting other cellular RING-motif proteins, such as the promyelocytic leukaemia protein PML. Altogether, the investigations described here illustrate the potential of the Z protein as a promising target for therapy and the prospects of the Z-reactive compounds to prevent arenavirus dissemination. © 2006 SGM.
format	JOUR
author	García, C.C. Djavani, M. Topisirovic, I. Borden, K.L.B. Salvato, M.S. Damonte, E.B.
author_facet	García, C.C. Djavani, M. Topisirovic, I. Borden, K.L.B. Salvato, M.S. Damonte, E.B.
author_sort	García, C.C.
title	Arenavirus Z protein as an antiviral target: Virus inactivation and protein oligomerization by zinc finger-reactive compounds
title_short	Arenavirus Z protein as an antiviral target: Virus inactivation and protein oligomerization by zinc finger-reactive compounds
title_full	Arenavirus Z protein as an antiviral target: Virus inactivation and protein oligomerization by zinc finger-reactive compounds
title_fullStr	Arenavirus Z protein as an antiviral target: Virus inactivation and protein oligomerization by zinc finger-reactive compounds
title_full_unstemmed	Arenavirus Z protein as an antiviral target: Virus inactivation and protein oligomerization by zinc finger-reactive compounds
title_sort	arenavirus z protein as an antiviral target: virus inactivation and protein oligomerization by zinc finger-reactive compounds
url	http://hdl.handle.net/20.500.12110/paper_00221317_v87_n5_p1217_Garcia
work_keys_str_mv	AT garciacc arenaviruszproteinasanantiviraltargetvirusinactivationandproteinoligomerizationbyzincfingerreactivecompounds AT djavanim arenaviruszproteinasanantiviraltargetvirusinactivationandproteinoligomerizationbyzincfingerreactivecompounds AT topisirovici arenaviruszproteinasanantiviraltargetvirusinactivationandproteinoligomerizationbyzincfingerreactivecompounds AT bordenklb arenaviruszproteinasanantiviraltargetvirusinactivationandproteinoligomerizationbyzincfingerreactivecompounds AT salvatoms arenaviruszproteinasanantiviraltargetvirusinactivationandproteinoligomerizationbyzincfingerreactivecompounds AT damonteeb arenaviruszproteinasanantiviraltargetvirusinactivationandproteinoligomerizationbyzincfingerreactivecompounds
_version_	1782030177570652160

Arenavirus Z protein as an antiviral target: Virus inactivation and protein oligomerization by zinc finger-reactive compounds

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