In vitro evaluation of antiviral activity of single and combined repurposable drugs against SARS-CoV-2

Antiviral Res. 2020 Sep;181:104878. doi: 10.1016/j.antiviral.2020.104878. Epub 2020 Jul 15.

Abstract

In response to the current pandemic caused by the novel SARS-CoV-2, identifying and validating effective therapeutic strategies is more than ever necessary. We evaluated the in vitro antiviral activities of a shortlist of compounds, known for their cellular broad-spectrum activities, together with drugs that are currently under evaluation in clinical trials for COVID-19 patients. We report the antiviral effect of remdesivir, lopinavir, chloroquine, umifenovir, berberine and cyclosporine A in Vero E6 cells model of SARS-CoV-2 infection, with estimated 50% inhibitory concentrations of 0.99, 5.2, 1.38, 3.5, 10.6 and 3 μM, respectively. Virus-directed plus host-directed drug combinations were also investigated. We report a strong antagonism between remdesivir and berberine, in contrast with remdesivir/diltiazem, for which we describe high levels of synergy, with mean Loewe synergy scores of 12 and peak values above 50. Combination of host-directed drugs with direct acting antivirals underscore further validation in more physiological models, yet they open up interesting avenues for the treatment of COVID-19.

Keywords: Antivirals; Berberine; COVID-19; Diltiazem; Drug combination; Remdesivir.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives
  • Adenosine Monophosphate / pharmacology
  • Alanine / analogs & derivatives
  • Alanine / pharmacology
  • Animals
  • Antiviral Agents / pharmacology*
  • Berberine / pharmacology
  • Betacoronavirus / drug effects*
  • COVID-19
  • Chlorocebus aethiops
  • Chloroquine / pharmacology
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / virology
  • Cyclosporine / pharmacology
  • Drug Antagonism
  • Drug Combinations
  • Drug Repositioning*
  • Drug Synergism
  • Humans
  • Indoles / pharmacology
  • Lopinavir / pharmacology
  • Pandemics*
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Vero Cells

Substances

  • Antiviral Agents
  • Drug Combinations
  • Indoles
  • Berberine
  • Lopinavir
  • remdesivir
  • Adenosine Monophosphate
  • Cyclosporine
  • Chloroquine
  • umifenovir
  • Alanine

Supplementary concepts

  • COVID-19 drug treatment