Phenotypical Screening of an MMV Open Box Library and Identification of Compounds with Antiviral Activity against St. Louis Encephalitis Virus

Autor(es)

Sotorilli, Giuliana Eboli ; Gravina, Humberto Doriguetto ; de Carvalho, Ana Carolina ; Shimizu, Jacqueline Farinha ; Fontoura, Marina Alves ; Melo-Hanchuk, Talita Diniz ; Cordeiro, Artur Torres ; Marques, Rafael Elias

• Tipo de documento: Artigo Científico
• Fonte: Viruses-Basel; v. 15, n. 12, p. 16-pg., 2023-12-01.

Resumo

St. Louis encephalitis virus (SLEV) is a neglected mosquito-borne Flavivirus that may cause severe neurological disease in humans and other animals. There are no specific treatments against SLEV infection or disease approved for human use, and drug repurposing may represent an opportunity to accelerate the development of treatments against SLEV. Here we present a scalable, medium-throughput phenotypic cell culture-based screening assay on Vero CCL81 cells to identify bioactive compounds that could be repurposed against SLEV infection. We screened eighty compounds from the Medicines for Malaria Venture (MMV) COVID Box library to identify nine (11%) compounds that protected cell cultures from SLEV-induced cytopathic effects, with low- to mid-micromolar potencies. We validated six hit compounds using viral plaque-forming assays to find that the compounds ABT-239, Amiodarone, Fluphenazine, Posaconazole, Triparanol, and Vidofludimus presented varied levels of antiviral activity and selectivity depending on the mammalian cell type used for testing. Importantly, we identified and validated the antiviral activity of the anti-flavivirus nucleoside analog 7DMA against SLEV. Triparanol and Fluphenazine reduced infectious viral loads in both Vero CCL81 and HBEC-5i cell cultures and, similar to the other validated compounds, are likely to exert antiviral activity through a molecular target in the host. (AU)

• Processo FAPESP: 18/10990-1 - Caracterização e potencial terapêutico de quimiocinas em sepse e encefalite induzida por Flavivirus
• Beneficiário: Rafael Elias Marques Pereira Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 21/05519-0 - Entendendo o papel do recrutamento e ativação de neutrófilos em doenças arbovirais
• Beneficiário: Rafael Elias Marques Pereira Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/02993-0 - Desenvolvimento do primeiro modelo experimental de infecção por Vírus Ilhéus (ILHV) em camundongos e delineamento de estratégias terapêuticas
• Beneficiário: Ana Carolina de Carvalho
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto