Platforms for Personalized Polytherapeutics Discovery in COVID-19

J Mol Biol. 2021 May 14;433(10):166945. doi: 10.1016/j.jmb.2021.166945. Epub 2021 Mar 20.

Abstract

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.

Keywords: ACE2; COVID-19; SARS-CoV; antiviral; combination therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • COVID-19 / economics
  • COVID-19 / genetics
  • COVID-19 Drug Treatment*
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / genetics
  • Disease Models, Animal*
  • Drug Evaluation, Preclinical / methods*
  • Humans
  • Induced Pluripotent Stem Cells / drug effects*
  • Zebrafish / genetics