Hesperidin Is a Potential Inhibitor against SARS-CoV-2 Infection

Nutrients. 2021 Aug 16;13(8):2800. doi: 10.3390/nu13082800.


Hesperidin (HD) is a common flavanone glycoside isolated from citrus fruits and possesses great potential for cardiovascular protection. Hesperetin (HT) is an aglycone metabolite of HD with high bioavailability. Through the docking simulation, HD and HT have shown their potential to bind to two cellular proteins: transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2), which are required for the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our results further found that HT and HD suppressed the infection of VeroE6 cells using lentiviral-based pseudo-particles with wild types and variants of SARS-CoV-2 with spike (S) proteins, by blocking the interaction between the S protein and cellular receptor ACE2 and reducing ACE2 and TMPRSS2 expression. In summary, hesperidin is a potential TMPRSS2 inhibitor for the reduction of the SARS-CoV-2 infection.

Keywords: 501Y.v2; ACE2; D614G; SARS-CoV-2; TMPRSS2; hesperidin.

MeSH terms

  • Angiotensin-Converting Enzyme 2 / chemistry
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Animals
  • COVID-19 / metabolism
  • COVID-19 / virology
  • COVID-19 Drug Treatment*
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Coronavirus Papain-Like Proteases / chemistry
  • Coronavirus Papain-Like Proteases / metabolism
  • Hesperidin / chemistry*
  • Hesperidin / pharmacology*
  • Humans
  • Molecular Docking Simulation
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / metabolism
  • Serine Endopeptidases / chemistry
  • Serine Endopeptidases / drug effects
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / metabolism
  • Vero Cells


  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Hesperidin
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human
  • Coronavirus Papain-Like Proteases
  • papain-like protease, SARS-CoV-2
  • hesperetin