Cargando…

Imidazonaphthyridine effects on Chikungunya virus replication: Antiviral activity by dependent and independent of interferon type 1 pathways

The Chikungunya virus (CHIKV) causes Chikungunya fever, a disease characterized by symptoms such as arthralgia/polyarthralgia. Currently, there are no antivirals approved against CHIKV, emphasizing the need to develop novel therapies. The imidazonaphthyridine compound (RO8191), an interferon-α (IFN-...

Descripción completa

Detalles Bibliográficos
Autores principales: Ruiz, Uriel Enrique Aquino, Santos, Igor Andrade, Grosche, Victória Riquena, Fernandes, Rafaela Sachetto, de Godoy, Andre Schutzer, Torres, Jhoan David Aguillón, Freire, Marjorie Caroline Liberato Cavalcanti, Mesquita, Nathalya Cristina de Moraes Roso, Guevara-Vega, Marco, Nicolau-Junior, Nilson, Sabino-Silva, Robinson, Mineo, Tiago Wilson Patriarca, Oliva, Glaucius, Jardim, Ana Carolina Gomes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10194360/
https://www.ncbi.nlm.nih.gov/pubmed/36565816
http://dx.doi.org/10.1016/j.virusres.2022.199029
_version_ 1785043999834243072
author Ruiz, Uriel Enrique Aquino
Santos, Igor Andrade
Grosche, Victória Riquena
Fernandes, Rafaela Sachetto
de Godoy, Andre Schutzer
Torres, Jhoan David Aguillón
Freire, Marjorie Caroline Liberato Cavalcanti
Mesquita, Nathalya Cristina de Moraes Roso
Guevara-Vega, Marco
Nicolau-Junior, Nilson
Sabino-Silva, Robinson
Mineo, Tiago Wilson Patriarca
Oliva, Glaucius
Jardim, Ana Carolina Gomes
author_facet Ruiz, Uriel Enrique Aquino
Santos, Igor Andrade
Grosche, Victória Riquena
Fernandes, Rafaela Sachetto
de Godoy, Andre Schutzer
Torres, Jhoan David Aguillón
Freire, Marjorie Caroline Liberato Cavalcanti
Mesquita, Nathalya Cristina de Moraes Roso
Guevara-Vega, Marco
Nicolau-Junior, Nilson
Sabino-Silva, Robinson
Mineo, Tiago Wilson Patriarca
Oliva, Glaucius
Jardim, Ana Carolina Gomes
author_sort Ruiz, Uriel Enrique Aquino
collection PubMed
description The Chikungunya virus (CHIKV) causes Chikungunya fever, a disease characterized by symptoms such as arthralgia/polyarthralgia. Currently, there are no antivirals approved against CHIKV, emphasizing the need to develop novel therapies. The imidazonaphthyridine compound (RO8191), an interferon-α (IFN-α) agonist, was reported as a potent inhibitor of HCV. Here RO8191 was investigated for its potential to inhibit CHIKV replication in vitro. RO8191 inhibited CHIKV infection in BHK-21 and Vero-E6 cells with a selectivity index (SI) of 12.3 and 37.3, respectively. Additionally, RO8191 was capable to protect cells against CHIKV infection, inhibit entry by virucidal activity, and strongly impair post-entry steps of viral replication. An effect of RO8191 on CHIKV replication was demonstrated in BHK-21 through type-1 IFN production mechanism and in Vero-E6 cells which has a defective type-1 IFN production, also suggesting a type-1 IFN independent mode of action. Molecular docking calculations demonstrated interactions of RO8191 with the CHIKV E proteins, corroborated by the ATR-FTIR assay, and with non-structural proteins, supported by the CHIKV-subgenomic replicon cells assay.
format Online
Article
Text
id pubmed-10194360
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-101943602023-05-19 Imidazonaphthyridine effects on Chikungunya virus replication: Antiviral activity by dependent and independent of interferon type 1 pathways Ruiz, Uriel Enrique Aquino Santos, Igor Andrade Grosche, Victória Riquena Fernandes, Rafaela Sachetto de Godoy, Andre Schutzer Torres, Jhoan David Aguillón Freire, Marjorie Caroline Liberato Cavalcanti Mesquita, Nathalya Cristina de Moraes Roso Guevara-Vega, Marco Nicolau-Junior, Nilson Sabino-Silva, Robinson Mineo, Tiago Wilson Patriarca Oliva, Glaucius Jardim, Ana Carolina Gomes Virus Res Article The Chikungunya virus (CHIKV) causes Chikungunya fever, a disease characterized by symptoms such as arthralgia/polyarthralgia. Currently, there are no antivirals approved against CHIKV, emphasizing the need to develop novel therapies. The imidazonaphthyridine compound (RO8191), an interferon-α (IFN-α) agonist, was reported as a potent inhibitor of HCV. Here RO8191 was investigated for its potential to inhibit CHIKV replication in vitro. RO8191 inhibited CHIKV infection in BHK-21 and Vero-E6 cells with a selectivity index (SI) of 12.3 and 37.3, respectively. Additionally, RO8191 was capable to protect cells against CHIKV infection, inhibit entry by virucidal activity, and strongly impair post-entry steps of viral replication. An effect of RO8191 on CHIKV replication was demonstrated in BHK-21 through type-1 IFN production mechanism and in Vero-E6 cells which has a defective type-1 IFN production, also suggesting a type-1 IFN independent mode of action. Molecular docking calculations demonstrated interactions of RO8191 with the CHIKV E proteins, corroborated by the ATR-FTIR assay, and with non-structural proteins, supported by the CHIKV-subgenomic replicon cells assay. Elsevier 2022-12-22 /pmc/articles/PMC10194360/ /pubmed/36565816 http://dx.doi.org/10.1016/j.virusres.2022.199029 Text en © 2022 The Authors. Published by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Ruiz, Uriel Enrique Aquino
Santos, Igor Andrade
Grosche, Victória Riquena
Fernandes, Rafaela Sachetto
de Godoy, Andre Schutzer
Torres, Jhoan David Aguillón
Freire, Marjorie Caroline Liberato Cavalcanti
Mesquita, Nathalya Cristina de Moraes Roso
Guevara-Vega, Marco
Nicolau-Junior, Nilson
Sabino-Silva, Robinson
Mineo, Tiago Wilson Patriarca
Oliva, Glaucius
Jardim, Ana Carolina Gomes
Imidazonaphthyridine effects on Chikungunya virus replication: Antiviral activity by dependent and independent of interferon type 1 pathways
title Imidazonaphthyridine effects on Chikungunya virus replication: Antiviral activity by dependent and independent of interferon type 1 pathways
title_full Imidazonaphthyridine effects on Chikungunya virus replication: Antiviral activity by dependent and independent of interferon type 1 pathways
title_fullStr Imidazonaphthyridine effects on Chikungunya virus replication: Antiviral activity by dependent and independent of interferon type 1 pathways
title_full_unstemmed Imidazonaphthyridine effects on Chikungunya virus replication: Antiviral activity by dependent and independent of interferon type 1 pathways
title_short Imidazonaphthyridine effects on Chikungunya virus replication: Antiviral activity by dependent and independent of interferon type 1 pathways
title_sort imidazonaphthyridine effects on chikungunya virus replication: antiviral activity by dependent and independent of interferon type 1 pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10194360/
https://www.ncbi.nlm.nih.gov/pubmed/36565816
http://dx.doi.org/10.1016/j.virusres.2022.199029
work_keys_str_mv AT ruizurielenriqueaquino imidazonaphthyridineeffectsonchikungunyavirusreplicationantiviralactivitybydependentandindependentofinterferontype1pathways
AT santosigorandrade imidazonaphthyridineeffectsonchikungunyavirusreplicationantiviralactivitybydependentandindependentofinterferontype1pathways
AT groschevictoriariquena imidazonaphthyridineeffectsonchikungunyavirusreplicationantiviralactivitybydependentandindependentofinterferontype1pathways
AT fernandesrafaelasachetto imidazonaphthyridineeffectsonchikungunyavirusreplicationantiviralactivitybydependentandindependentofinterferontype1pathways
AT degodoyandreschutzer imidazonaphthyridineeffectsonchikungunyavirusreplicationantiviralactivitybydependentandindependentofinterferontype1pathways
AT torresjhoandavidaguillon imidazonaphthyridineeffectsonchikungunyavirusreplicationantiviralactivitybydependentandindependentofinterferontype1pathways
AT freiremarjoriecarolineliberatocavalcanti imidazonaphthyridineeffectsonchikungunyavirusreplicationantiviralactivitybydependentandindependentofinterferontype1pathways
AT mesquitanathalyacristinademoraesroso imidazonaphthyridineeffectsonchikungunyavirusreplicationantiviralactivitybydependentandindependentofinterferontype1pathways
AT guevaravegamarco imidazonaphthyridineeffectsonchikungunyavirusreplicationantiviralactivitybydependentandindependentofinterferontype1pathways
AT nicolaujuniornilson imidazonaphthyridineeffectsonchikungunyavirusreplicationantiviralactivitybydependentandindependentofinterferontype1pathways
AT sabinosilvarobinson imidazonaphthyridineeffectsonchikungunyavirusreplicationantiviralactivitybydependentandindependentofinterferontype1pathways
AT mineotiagowilsonpatriarca imidazonaphthyridineeffectsonchikungunyavirusreplicationantiviralactivitybydependentandindependentofinterferontype1pathways
AT olivaglaucius imidazonaphthyridineeffectsonchikungunyavirusreplicationantiviralactivitybydependentandindependentofinterferontype1pathways
AT jardimanacarolinagomes imidazonaphthyridineeffectsonchikungunyavirusreplicationantiviralactivitybydependentandindependentofinterferontype1pathways