Platforms for Personalized Polytherapeutics Discovery in COVID-19

Area of Science:

• Virology
• Pharmacology
• Biotechnology

Background:

• The COVID-19 pandemic's third wave intensified in November 2020.
• Severe complications from SARS-CoV-2 infection necessitate novel treatment strategies.
• Existing therapeutic approaches require augmentation to manage disease severity.

Purpose of the Study:

• To advocate for combination therapies (polytherapeutics) as a critical strategy against SARS-CoV-2.
• To outline essential systems for efficient combinatorial assessment of therapeutic candidates.
• To propose innovative platforms for modeling and screening COVID-19 treatments.

Main Methods:

• Micro-physiological systems utilizing human induced pluripotent stem cells (iPSC) for tissue-specific infection modeling.
• Gene-humanized zebrafish and Caenorhabditis elegans (C. elegans) for high-throughput combinatorial drug screening.
• Engineered pseudo-typing systems for safe modeling of SARS-CoV-2 infection in experimental models.

Main Results:

• Identified the need for advanced systems to accelerate the evaluation of combination therapies.
• Demonstrated the potential of iPSC-based models for studying tissue-specific SARS-CoV-2 pathology.
• Highlighted the utility of genetically modified model organisms for large-scale drug screening.
• Proposed safe methods for in vivo and in vitro infection modeling.

Conclusions:

• Combination therapies represent a vital approach to managing severe COVID-19.
• Advanced in vitro and in vivo systems are essential for the rapid development and assessment of polytherapeutics.
• Integrating micro-physiological systems, model organisms, and engineered safety systems can expedite the discovery of effective COVID-19 treatments.