The PIKfyve Inhibitor Apilimod: A Double-Edged Sword against COVID-19

Cells. 2020 Dec 27;10(1):30. doi: 10.3390/cells10010030.

Abstract

The PIKfyve inhibitor apilimod is currently undergoing clinical trials for treatment of COVID-19. However, although apilimod might prevent viral invasion by inhibiting host cell proteases, the same proteases are critical for antigen presentation leading to T cell activation and there is good evidence from both in vitro studies and the clinic that apilimod blocks antiviral immune responses. We therefore warn that the immunosuppression observed in many COVID-19 patients might be aggravated by apilimod.

Keywords: COVID-19; LAM-002A; PIKfyve; SARS-CoV-2; STA-5326; apilimod.

MeSH terms

  • Antiviral Agents / adverse effects*
  • Antiviral Agents / pharmacology
  • COVID-19 / drug therapy*
  • COVID-19 / immunology
  • Humans
  • Hydrazones / adverse effects*
  • Hydrazones / pharmacology
  • Morpholines / adverse effects*
  • Morpholines / pharmacology
  • Peptide Hydrolases / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors / adverse effects*
  • Phosphoinositide-3 Kinase Inhibitors / pharmacology
  • Protease Inhibitors / pharmacology
  • Pyrimidines / adverse effects*
  • Pyrimidines / pharmacology
  • SARS-CoV-2 / drug effects*
  • Serine Endopeptidases / metabolism

Substances

  • Antiviral Agents
  • Hydrazones
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Protease Inhibitors
  • Pyrimidines
  • PIKFYVE protein, human
  • Peptide Hydrolases
  • Serine Endopeptidases
  • transmembrane serine protease 2, human
  • apilimod