Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro

Antiviral Res. 2020 Jun;178:104786. doi: 10.1016/j.antiviral.2020.104786. Epub 2020 Apr 3.

Abstract

An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 μM, 26.63 μM, 2.55 μM and 0.46 μM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 μM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 μM in combination with emetine at 0.195 μM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.

Keywords: ABSTRACT; COVID-19; Emetine; Homoharringtonine; Lopinavir; Remdesivir; Ritonavir.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives
  • Alanine / analogs & derivatives
  • Amides / pharmacology
  • Animals
  • Antimetabolites / pharmacology*
  • Antiviral Agents / pharmacology*
  • Betacoronavirus / drug effects*
  • Betacoronavirus / physiology
  • COVID-19
  • Chlorocebus aethiops
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / virology*
  • Drug Combinations
  • Emetine / pharmacology*
  • Epithelial Cells
  • Homoharringtonine / pharmacology*
  • Humans
  • Lopinavir / pharmacology*
  • Pandemics
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / virology*
  • Pyrazines / pharmacology
  • Ribavirin / pharmacology
  • SARS-CoV-2
  • Vero Cells
  • Virus Replication / drug effects*

Substances

  • Amides
  • Antimetabolites
  • Antiviral Agents
  • Drug Combinations
  • Pyrazines
  • Lopinavir
  • remdesivir
  • Adenosine Monophosphate
  • Ribavirin
  • Homoharringtonine
  • favipiravir
  • Alanine
  • Emetine

Supplementary concepts

  • COVID-19 drug treatment