Repositioning of Ligands That Target the Spike Glycoprotein as Potential Drugs for SARS-CoV-2 in an In Silico Study

Molecules. 2020 Nov 29;25(23):5615. doi: 10.3390/molecules25235615.


The worldwide health emergency of the SARS-CoV-2 pandemic and the absence of a specific treatment for this new coronavirus have led to the use of computational strategies (drug repositioning) to search for treatments. The aim of this work is to identify FDA (Food and Drug Administration)-approved drugs with the potential for binding to the spike structural glycoprotein at the hinge site, receptor binding motif (RBM), and fusion peptide (FP) using molecular docking simulations. Drugs that bind to amino acids are crucial for conformational changes, receptor recognition, and fusion of the viral membrane with the cell membrane. The results revealed some drugs that bind to hinge site amino acids (varenicline, or steroids such as betamethasone while other drugs bind to crucial amino acids in the RBM (naldemedine, atovaquone, cefotetan) or FP (azilsartan, maraviroc, and difluprednate); saquinavir binds both the RBM and the FP. Therefore, these drugs could inhibit spike glycoprotein and prevent viral entry as possible anti-COVID-19 drugs. Several drugs are in clinical studies; by focusing on other pharmacological agents (candesartan, atovaquone, losartan, maviroc and ritonavir) in this work we propose an additional target: the spike glycoprotein. These results can impact the proposed use of treatments that inhibit the first steps of the virus replication cycle.

Keywords: COVID-19; FDA-approved drugs; SARS-CoV-2; docking studies; spike glycoprotein.

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Computer Simulation
  • Drug Repositioning / methods*
  • Ligands
  • Membrane Fusion / drug effects
  • Models, Molecular
  • Molecular Docking Simulation
  • Protein Conformation
  • Spike Glycoprotein, Coronavirus / chemistry*
  • Spike Glycoprotein, Coronavirus / metabolism
  • Varenicline / chemistry
  • Varenicline / metabolism
  • Varenicline / pharmacology


  • Antiviral Agents
  • Ligands
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Varenicline

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