Characterization and Treatment of SARS-CoV-2 in Nasal and Bronchial Human Airway Epithelia

Cell Rep Med. 2020 Jul 21;1(4):100059. doi: 10.1016/j.xcrm.2020.100059.


In the current COVID-19 pandemic context, proposing and validating effective treatments represents a major challenge. However, the scarcity of biologically relevant pre-clinical models of SARS-CoV-2 infection imposes a significant barrier for scientific and medical progress, including the rapid transition of potentially effective treatments to the clinical setting. We use reconstituted human airway epithelia to isolate and then characterize the viral infection kinetics, tissue-level remodeling of the cellular ultrastructure, and transcriptional early immune signatures induced by SARS-CoV-2 in a physiologically relevant model. Our results emphasize distinctive transcriptional immune signatures between nasal and bronchial HAE, both in terms of kinetics and intensity, hence suggesting putative intrinsic differences in the early response to SARS-CoV-2 infection. Most important, we provide evidence in human-derived tissues on the antiviral efficacy of remdesivir monotherapy and explore the potential of the remdesivir-diltiazem combination as an option worthy of further investigation to respond to the still-unmet COVID-19 medical need.

Keywords: COVID-19; SARS-CoV-2; cell ultrastructure remodeling; coronavirus; diltiazem; drug combination; innate immune response; remdesivir; repurposing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives
  • Adenosine Monophosphate / pharmacology
  • Airway Remodeling
  • Alanine / analogs & derivatives
  • Alanine / pharmacology
  • Animals
  • Antiviral Agents / pharmacology*
  • Bronchi / drug effects
  • Bronchi / immunology
  • Bronchi / ultrastructure
  • Bronchi / virology*
  • COVID-19 / immunology
  • COVID-19 / pathology
  • COVID-19 / virology
  • COVID-19 Drug Treatment
  • Chlorocebus aethiops
  • Diltiazem / pharmacology
  • Drug Synergism
  • Humans
  • Immunity, Innate
  • Models, Biological
  • Nose / drug effects
  • Nose / immunology
  • Nose / ultrastructure
  • Nose / virology*
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / ultrastructure
  • Respiratory Mucosa / virology*
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / growth & development
  • Vero Cells


  • Antiviral Agents
  • remdesivir
  • Adenosine Monophosphate
  • Diltiazem
  • Alanine