01609nas a2200313   4500000000100000000000100001008004100002260001500043653000900058653001300067653001300080653001400093653002400107100002400131700002000155700002100175700002300196700002200219700001900241700002100260700002000281700002100301245007000322856007200392300001100464490000800475520079800483022001401281       2021                            d  c2021-05-1410aACE210aCOVID-1910aSARS-CoV10aantiviral10acombination therapy1 aChristopher Hopkins1 aChidinma Onweni1 aVictoria Zambito1 aDeLisa Fairweather1 aKathryn McCormick1 aHideki Ebihara1 aThomas Caulfield1 aYu Shrike Zhang1 aW. David Freeman00aPlatforms for Personalized Polytherapeutics Discovery in COVID-19  uhttps://www.sciencedirect.com/science/article/pii/S0022283621001467  a1669450 v4333 aThe COVID-19 pandemic entered its third and most intense to date wave of infections in November 2020. This perspective article describes how combination therapies (polytherapeutics) are a needed focus for helping battle the severity of complications from SARS-CoV-2 infection. It outlines the types of systems that are needed for fast and efficient combinatorial assessment of therapeutic candidates. Proposed are micro-physiological systems using human iPSC as a format for tissue-specific modeling of infection, the use of gene-humanized zebrafish and C. elegans for combinatorial drug screens due to the animals being addressable in liquid multi-well formats, and the use of engineered pseudo-typing systems to safely model infection in the transgenic animals and engineered tissue systems.  a0022-2836