Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Virus research, 2023-01, Vol.324, p.199029-199029, Article 199029

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• •RO8191 strongly inhibits CHIKV replication in cells with defective type-1 IFN production.•RO8191 inhibited multiple stages of CHIKV replication cycle.•The highest antiviral activity was in the virucidal and post-entry stages.•Molecular docking analyses showed interactions between imidazonaphthyridine and CHIKV proteins.•ATR-FTIR analysis showed interactions mainly between RO8191 and CHIKV glycoproteins.•Our data suggest an in vitro antiviral activity of RO8191 against CHIKV. 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.