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Next-Generation Phenotypic Screening in Early Drug Discovery for Infectious Diseases
Nathalie Aulner1, Anne Danckaert1, JongEun Ihm1
1Institut Pasteur Paris, UTechS-PBI/Imagopole, 25-28 rue du Docteur Roux, 75015, France.
Abstract:
Cell-based phenotypic screening has proven to be valuable, notably in recapitulating relevant biological conditions, for example, the host cell/pathogen niche. However, the corresponding methodological complexity is not readily compatible with high-throughput pipelines, and fails to inform either molecular target or mechanism of action, which frustrates conventional drug-discovery roadmaps. We review the state-of-the-art and emerging technologies that suggest new strategies for harnessing value from the complexity of phenotypic screening and augmenting powerful utility for translational drug discovery. Advances in cellular, molecular, and bioinformatics technologies are converging at a cutting edge where the complexity of phenotypic screening may no longer be considered a hinderance but rather a catalyst to chemotherapeutic discovery for infectious diseases.
Insights
Cell-based phenotypic screening offers valuable biological insights but faces high-throughput challenges. Emerging technologies can overcome complexity, accelerating drug discovery for infectious diseases.
Area of Science:
- Drug discovery and development
- Cell biology
- Infectious diseases
Background:
- Cell-based phenotypic screening is valuable for modeling biological conditions like host-pathogen interactions.
- Its methodological complexity limits high-throughput application and target identification, hindering conventional drug discovery.
Purpose of the Study:
- To review current and emerging technologies for phenotypic screening.
- To explore strategies for leveraging screening complexity in drug discovery.
- To enhance the utility of phenotypic screening for translational drug discovery.
Main Methods:
- Review of state-of-the-art and emerging technologies in cellular, molecular, and bioinformatics.
- Analysis of how these advances address the limitations of traditional phenotypic screening.
Main Results:
- Advances in cellular, molecular, and bioinformatics are converging.
- These technologies offer new strategies to harness the complexity of phenotypic screening.
- Phenotypic screening complexity can be transformed from a hindrance into a catalyst for discovery.
Conclusions:
- Emerging technologies can overcome the limitations of traditional phenotypic screening.
- Complexity in phenotypic screening can be leveraged for more effective drug discovery.
- This approach holds significant promise for developing new chemotherapeutics for infectious diseases.
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