Broadly Active Antiviral Compounds Disturb Zika Virus Progeny Release Rescuing Virus-Induced Toxicity in Brain Organoids
Abstract
:1. Introduction
2. Materials and Methods
2.1. Biosafety
2.2. Cells and Viruses
2.3. Virus Inoculation and Compound Treatments
2.4. Phenotypic Antiviral Assay
2.5. Determining Antiviral and Cytotoxicity EC50
2.6. Virus Infectivity Assay
2.7. End-Point Dilution Assay by Immunofluorescence
2.8. End-Point Dilution Assay by CPE
2.9. High-Throughput Microscopy
2.10. Z-Factor Calculations
2.11. Generation of Human Cerebral Organoids from hiPS Cells and ZIKV Infection
2.12. Immunohistochemistry
2.13. Immunofluorescence Imaging
2.14. RNA Isolation and Real-Time Quantitative PCR
2.15. Cell Viability Assays
2.16. Organoid Viability Assay
2.17. Time Course and Time-of-Addition Assays
2.18. Viral Budding Assay
2.19. Synthesis of Compounds
2.20. Statistical Analysis
2.21. Ethics Statement
3. Results
3.1. TH3289 and TH6744 Shows Antiviral Activity against ZIKV
3.2. Novel Antiviral Compounds Have a Similar Therapeutic Window as Ribavirin against ZIKV in Cellular Models
3.3. TH6744 and TH5487 Treatment Reverses ZIKV-Induced Neurotoxicity and Limits ZIKV Propagation in a 3D Cerebral Organoid Model
3.4. TH6744 Disturbs Late Steps in ZIKV Life Cycle
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Pettke, A.; Tampere, M.; Pronk, R.; Wallner, O.; Falk, A.; Warpman Berglund, U.; Helleday, T.; Mirazimi, A.; Puumalainen, M.-R. Broadly Active Antiviral Compounds Disturb Zika Virus Progeny Release Rescuing Virus-Induced Toxicity in Brain Organoids. Viruses 2021, 13, 37. https://doi.org/10.3390/v13010037
Pettke A, Tampere M, Pronk R, Wallner O, Falk A, Warpman Berglund U, Helleday T, Mirazimi A, Puumalainen M-R. Broadly Active Antiviral Compounds Disturb Zika Virus Progeny Release Rescuing Virus-Induced Toxicity in Brain Organoids. Viruses. 2021; 13(1):37. https://doi.org/10.3390/v13010037
Chicago/Turabian StylePettke, Aleksandra, Marianna Tampere, Robin Pronk, Olov Wallner, Anna Falk, Ulrika Warpman Berglund, Thomas Helleday, Ali Mirazimi, and Marjo-Riitta Puumalainen. 2021. "Broadly Active Antiviral Compounds Disturb Zika Virus Progeny Release Rescuing Virus-Induced Toxicity in Brain Organoids" Viruses 13, no. 1: 37. https://doi.org/10.3390/v13010037
APA StylePettke, A., Tampere, M., Pronk, R., Wallner, O., Falk, A., Warpman Berglund, U., Helleday, T., Mirazimi, A., & Puumalainen, M. -R. (2021). Broadly Active Antiviral Compounds Disturb Zika Virus Progeny Release Rescuing Virus-Induced Toxicity in Brain Organoids. Viruses, 13(1), 37. https://doi.org/10.3390/v13010037