In silico Potential of Approved Antimalarial Drugs for Repurposing Against COVID-19

OMICS. 2020 Oct;24(10):568-580. doi: 10.1089/omi.2020.0071. Epub 2020 Jul 30.


Although the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is wreaking havoc and resulting in mortality and morbidity across the planet, novel treatments are urgently needed. Drug repurposing offers an innovative approach in this context. We report here new findings on the in silico potential of several antimalarial drugs for repurposing against COVID-19. We conducted analyses by docking the compounds against two SARS-CoV-2-specific targets: (1) the receptor binding domain spike protein and (2) the main protease of the virus (MPro) using the Schrödinger software. Importantly, the docking analysis revealed that doxycycline (DOX) showed the most effective binding to the spike protein of SARS-CoV-2, whereas halofantrine and mefloquine bound effectively with the main protease among the antimalarial drugs evaluated in the present study. The in silico approach reported here suggested that DOX could potentially be a good candidate for repurposing for COVID-19. In contrast, to decipher the actual potential of DOX and halofantrine against COVID-19, further in vitro and in vivo studies are called for. Drug repurposing warrants consideration as a viable research and innovation avenue as planetary health efforts to fight the COVID-19 continue.

Keywords: COVID-19; SARS-CoV-2; antimalarial drugs; drug development; drug repurposing; planetary health.

MeSH terms

  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Betacoronavirus / chemistry
  • Betacoronavirus / drug effects*
  • Binding Sites
  • COVID-19
  • COVID-19 Drug Treatment
  • Computer Simulation
  • Coronavirus 3C Proteases
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / epidemiology
  • Coronavirus Infections / virology
  • Cysteine Endopeptidases / chemistry
  • Cysteine Endopeptidases / drug effects
  • Doxycycline / chemistry
  • Doxycycline / pharmacology
  • Drug Evaluation, Preclinical
  • Drug Repositioning / methods*
  • Humans
  • Molecular Docking Simulation
  • Pandemics
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / epidemiology
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / drug effects
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / drug effects


  • Antimalarials
  • Antiviral Agents
  • Spike Glycoprotein, Coronavirus
  • Viral Nonstructural Proteins
  • spike protein, SARS-CoV-2
  • Cysteine Endopeptidases
  • Coronavirus 3C Proteases
  • Doxycycline