The anti-HIV drug nelfinavir mesylate (Viracept) is a potent inhibitor of cell fusion caused by the SARSCoV-2 spike (S) glycoprotein warranting further evaluation as an antiviral against COVID-19 infections

J Med Virol. 2020 Oct;92(10):2087-2095. doi: 10.1002/jmv.25985. Epub 2020 May 17.


Severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) is the causative agent of the coronavirus disease-2019 (COVID-19) pandemic. Coronaviruses enter cells via fusion of the viral envelope with the plasma membrane and/or via fusion of the viral envelope with endosomal membranes after virion endocytosis. The spike (S) glycoprotein is a major determinant of virus infectivity. Herein, we show that the transient expression of the SARS CoV-2 S glycoprotein in Vero cells caused extensive cell fusion (formation of syncytia) in comparison to limited cell fusion caused by the SARS S glycoprotein. Both S glycoproteins were detected intracellularly and on transfected Vero cell surfaces. These results are in agreement with published pathology observations of extensive syncytia formation in lung tissues of patients with COVID-19. These results suggest that SARS CoV-2 is able to spread from cell-to-cell much more efficiently than SARS effectively avoiding extracellular neutralizing antibodies. A systematic screening of several drugs including cardiac glycosides and kinase inhibitors and inhibitors of human immunodeficiency virus (HIV) entry revealed that only the FDA-approved HIV protease inhibitor, nelfinavir mesylate (Viracept) drastically inhibited S-n- and S-o-mediated cell fusion with complete inhibition at a 10-μM concentration. In-silico docking experiments suggested the possibility that nelfinavir may bind inside the S trimer structure, proximal to the S2 amino terminus directly inhibiting S-n- and S-o-mediated membrane fusion. Also, it is possible that nelfinavir may act to inhibit S proteolytic processing within cells. These results warrant further investigations of the potential of nelfinavir mesylate to inhibit virus spread at early times after SARS CoV-2 symptoms appear.

Keywords: SARS coronavirus; antiviral agents; cell fusion; cellular effect; coronavirus; entry inhibitors; fusion protein; glycoproteins; infection; virus classification.

Publication types

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

MeSH terms

  • Animals
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Binding Sites
  • COVID-19 Drug Treatment
  • Cell Fusion
  • Chlorocebus aethiops
  • Giant Cells / drug effects
  • Giant Cells / pathology
  • Giant Cells / virology
  • Humans
  • Membrane Fusion / drug effects*
  • Molecular Docking Simulation
  • Nelfinavir / chemistry
  • Nelfinavir / pharmacology*
  • Plasmids / chemistry
  • Plasmids / metabolism
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / pathogenicity
  • SARS-CoV-2 / physiology
  • Severe acute respiratory syndrome-related coronavirus / drug effects*
  • Severe acute respiratory syndrome-related coronavirus / pathogenicity
  • Severe acute respiratory syndrome-related coronavirus / physiology
  • Spike Glycoprotein, Coronavirus / antagonists & inhibitors*
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / metabolism
  • Vero Cells
  • Virion / drug effects
  • Virion / pathogenicity
  • Virion / physiology


  • Anti-HIV Agents
  • Recombinant Proteins
  • Spike Glycoprotein, Coronavirus
  • spike glycoprotein, SARS-CoV
  • spike protein, SARS-CoV-2
  • Nelfinavir