Ivermectin Docks to the SARS-CoV-2 Spike Receptor-binding Domain Attached to ACE2

In Vivo. Sep-Oct 2020;34(5):3023-3026. doi: 10.21873/invivo.12134.

Abstract

Background/aim: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One drug that has attracted interest is the antiparasitic compound ivermectin, a macrocyclic lactone derived from the bacterium Streptomyces avermitilis. We carried out a docking study to determine if ivermectin might be able to attach to the SARS-CoV-2 spike receptor-binding domain bound with ACE2.

Materials and methods: We used the program AutoDock Vina Extended to perform the docking study.

Results: Ivermectin docked in the region of leucine 91 of the spike and histidine 378 of the ACE2 receptor. The binding energy of ivermectin to the spike-ACE2 complex was -18 kcal/mol and binding constant was 5.8 e-08.

Conclusion: The ivermectin docking we identified may interfere with the attachment of the spike to the human cell membrane. Clinical trials now underway should determine whether ivermectin is an effective treatment for SARS-Cov2 infection.

Keywords: ACE2; COVID-19; ivermectin; spike protein.

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Betacoronavirus / chemistry
  • Betacoronavirus / drug effects*
  • Betacoronavirus / pathogenicity
  • Binding Sites / drug effects
  • COVID-19
  • Cell Membrane / drug effects
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / virology
  • Drug Repositioning
  • Histidine / chemistry
  • Humans
  • Ivermectin / chemistry*
  • Ivermectin / therapeutic use
  • Leucine / chemistry
  • Molecular Docking Simulation
  • Pandemics
  • Peptidyl-Dipeptidase A / chemistry*
  • Peptidyl-Dipeptidase A / drug effects
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Streptomyces / chemistry

Substances

  • Histidine
  • Ivermectin
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Leucine

Supplementary concepts

  • Streptomyces avermitilis