Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19)

Viruses. 2020 Jun 10;12(6):628. doi: 10.3390/v12060628.


The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signals an urgent need for an expansion in treatment options. In this study, we investigated the anti-SARS-CoV-2 activities of 22 antiviral agents with known broad-spectrum antiviral activities against coronaviruses and/or other viruses. They were first evaluated in our primary screening in VeroE6 cells and then the most potent anti-SARS-CoV-2 antiviral agents were further evaluated using viral antigen expression, viral load reduction, and plaque reduction assays. In addition to remdesivir, lopinavir, and chloroquine, our primary screening additionally identified types I and II recombinant interferons, 25-hydroxycholesterol, and AM580 as the most potent anti-SARS-CoV-2 agents among the 22 antiviral agents. Betaferon (interferon-β1b) exhibited the most potent anti-SARS-CoV-2 activity in viral antigen expression, viral load reduction, and plaque reduction assays among the recombinant interferons. The lipogenesis modulators 25-hydroxycholesterol and AM580 exhibited EC50 at low micromolar levels and selectivity indices of >10.0. Combinational use of these host-based antiviral agents with virus-based antivirals to target different processes of the SARS-CoV-2 replication cycle should be evaluated in animal models and/or clinical trials.

Keywords: 25-hydroxycholesterol; AM580; COVID-19; coronavirus; interferon; treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Viral / immunology
  • Antiviral Agents / pharmacology*
  • Betacoronavirus / drug effects*
  • Betacoronavirus / immunology
  • Betacoronavirus / metabolism
  • COVID-19
  • Chlorocebus aethiops
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / virology
  • Humans
  • Interferons / metabolism
  • Lipogenesis / drug effects
  • Pandemics
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Signal Transduction / drug effects
  • Vero Cells
  • Viral Load / drug effects
  • Viral Plaque Assay
  • Virus Replication / drug effects


  • Antigens, Viral
  • Antiviral Agents
  • Interferons