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

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Ruiz, Uriel Enrique Aquino ; Santos, Igor Andrade ; Grosche, Victoria Riquena ; Fernandes, Rafaela Sachetto ; Godoy, Andre Schutzer de ; Torres, Jhoan David Aguillon ; 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

• Tipo de documento: Artigo Científico
• Fonte: VIRUS RESEARCH; v. 324, p. 14-pg., 2023-01-03.

Resumo

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-alpha (IFN-alpha) agonist, was reported as a potent inhibitor of HCV. Here RO8191 was investigated for its potential to inhibit CHIKV repli-cation 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. (AU)

• Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
• Beneficiário: Glaucius Oliva
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 16/19712-9 - Caracterização estrutural das proteínas do vírus Zika e busca por agentes antivirais
• Beneficiário: Andre Schutzer de Godoy
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/05130-3 - Construção e caracterização de um sistema replicon sub-genômico do ZIKV para a descoberta de agentes antivirais.
• Beneficiário: Rafaela Sachetto Fernandes
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado