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A Multi-Phenotype System to Discover Therapies for Age-Related Dysregulation of the Immune Response to Viral Infections

By Brandon White, Ben Komalo, Lauren Nicolaisen, Matt Donne, Charlie Marsh, Rachel M DeVay, An M Nguyen, Wendy Cousin, Jarred Heinrich, William J Van Trump, Tempest Plott, Colin J. Fuller, Dat Nguyen, Daniel Chen, Delia Bucher, Sabine Tyrra, Laura Haynes, George Kuchel, Jorg Goronzy, Anis Larbi, Tamas Fulop, Diane Heiser, Ralf Schwandner, Christian Elabd, Ben Kamens

Posted 30 Jul 2020
bioRxiv DOI: 10.1101/2020.07.30.223875

Age-related immune dysregulation contributes to increased susceptibility to infection and disease in older adults. We combined high-throughput laboratory automation with machine learning to build a multi-phenotype aging profile that models the dysfunctional immune response to viral infection in older adults. From a single well, our multi-phenotype aging profile can capture changes in cell composition, physical cell-to-cell interaction, organelle structure, cytokines, and other hidden complexities contributing to age-related dysfunction. This system allows for rapid identification of new potential compounds to rejuvenate older adults' immune response. We used our technology to screen thousands of compounds for their ability to make old immune cells respond to viral infection like young immune cells. We observed beneficial effects of multiple compounds, of which two of the most promising were disulfiram and triptonide. Our findings indicate that disulfiram could be considered as a treatment for severe coronavirus disease 2019 and other inflammatory infections. ### Competing Interest Statement Brandon White, Ben Komalo, Lauren Nicolaisen, Matt Donne, Charlie Marsh, Rachel M. DeVay, An M. Nguyen, Wendy Cousin, Jarred Heinrich, William Van Trump, Tempest Plott, Colin J. Fuller, Dat Nguyen, Daniel Chen, Christian Elabd, and Ben Kamens are employees of, and have an equity interest in, Spring Discovery. Brandon White, Ben Komalo, Lauren Nicolaisen, Charlie Marsh, An M. Nguyen, Wendy Cousin, Christian Elabd, and Ben Kamens are co-inventors on patents filed for this work and pending to Spring Discovery. Laura Haynes and Jorg Goronzy report grants from NIH. Laura Haynes, George Kuchel, Jorg Goronzy, Anis Larbi, and Ralf Schwandner report personal fees from Spring Discovery. Anis Larbi is the co-founder of Yobitrust. Ralf Schwandner is the founder and CEO of Assay.Works GmBH. Delia Bucher, Sabine Tyrra, Tamas Fulop, and Diane Heiser have nothing to disclose.

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