Platforms for Personalized Polytherapeutics Discovery in COVID-19

Christopher Hopkins, Chidinma Onweni, Victoria Zambito, De Lisa Fairweather, Kathryn McCormick, Hideki Ebihara, Tom Caulfield, Yu Shrike Zhang, W. David Freeman

Research output: Contribution to journalReview articlepeer-review


The 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.

Original languageEnglish (US)
Article number166945
JournalJournal of Molecular Biology
Issue number10
StatePublished - May 14 2021


  • ACE2
  • COVID-19
  • SARS-CoV
  • antiviral
  • combination therapy

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Molecular Biology


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