The PI3K/Akt/mTOR pathway: A potential pharmacological target in COVID-19

Drug Discov Today. 2022 Mar;27(3):848-856. doi: 10.1016/j.drudis.2021.11.002. Epub 2021 Nov 8.

Abstract

Coronavirus disease 2019 (COVID-19) has emerged as a serious threat to global health. The disregulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) cell signaling pathway observed in patients with COVID-19 has attracted attention for the possible use of specific inhibitors of this pathway for the treatment of the disease. Here, we review emerging data on the involvement of the PI3K/Akt/mTOR pathway in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the clinical studies investigating its tailored inhibition in COVID-19. Current in silico, in vitro, and in vivo data convergently support a role for the PI3K/Akt/mTOR pathway in COVID-19 and suggest the use of specific inhibitors of this pathway that, by a combined mechanism entailing downregulation of excessive inflammatory reactions, cell protection, and antiviral effects, could ameliorate the course of COVID-19.

Keywords: Akt inhibitors; COVID-19; PI3K inhibitors; PI3K/Akt/mTOR pathway; SARS-CoV-2; mTOR inhibitors.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • COVID-19 / metabolism
  • COVID-19 Drug Treatment*
  • Humans
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Antiviral Agents
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases