Drug screening against Yellow fever Virus Lucio Freitas Junior - - PowerPoint PPT Presentation
Drug screening against Yellow fever Virus Lucio Freitas Junior Departamento de Micorbiologia Instituto de Cincias Biomdicas Universidade de So Paulo The Phenotypic Screening Platform at ICB-USP Chemical and Genetic screening
Lucio Freitas Junior
Departamento de Micorbiologia Instituto de Ciências Biomédicas Universidade de São Paulo
Chemical and Genetic screening
Chagas disease Leishmaniasis Worms Zika Chikungunya Dengue Yellow Fever
Cellular models of disease Phenotypic assays
Secondary assays for hit MoA and target deconvolution
Huh7 cels + ZIKV or YFV + compound 72 h incubation at 37 oC and 5% C02 Fixation and labeling of with DAPI and with Anti-Flavivirus antibody Reading Data analysis
Ensaio Hits Lead Pré-clínico Fase I
Activity Relationship (SAR)
(preliminar)
MEDICINAL CHEMISTRY BIOLOGY DRUG METABOLISM & PHARMACOKINETICS SCREENING LAB
Input Image
YFV
Nuclei Selection
YFV
Cytoplasm Selection
YFV
Select Population I
YFV
Alexa Intensity
YFV
Infected cells
YFV
Screening of a FDA-approved drug library for inhibitors of Y fever virus infection in human cells
Compound Max activity (%) EC50 (mg/mL) CC50 (mg/mL) S.I. Sofosbuvir 100.07 0.0013 ND 307.665
SOFOSBUVIR
50 100 150
0.0 0.5 1.0 1.5
log [Cpd], mg/mL
Normalized Activity % Cell Ratio
Yellow fever assay
Compound Max activity (%) EC50 (mg/mL) CC50 (mg/mL) S.I. Harvoni 100.07 0.0002 0.1089 659.04
HARVONI
50 100 150
0.0 0.5 1.0 1.5
log [Cpd], mg/mL
Normalized Activity % Cell Ratio
Yellow fever assay
Department of Microbiology Luís Carlos de Souza Ferreira Marcia Mayer Gabriel Padilla Paolo Zanotto Edison Durigon Joao Renato Rebello Sergio Schenkman
Phenotypic Screening Platform
Carolina Borsoi Moraes Adalberto Araujo-Junior Caio H. Franco Luisa Naves Laura Alcantara Denise Pilger Rafaela Bonotto Giovana Cintra Bruna Wey
luciofreitasjunior@gmail.com