Overexpression of estrogen receptor GPER1 and G1 treatment reduces SARS-CoV-2 infection in BEAS-2B bronchial cells

Mol Cell Endocrinol. 2022 Dec 1:558:111775. doi: 10.1016/j.mce.2022.111775. Epub 2022 Sep 9.

Abstract

Gender-bias in COVID-19 severity has been suggested by clinical data. Experimental data in cell and animal models have demonstrated the role of sex hormones, particularly estrogens, in viral infections such as in COVID-19. SARS-CoV-2 uses ACE2 as a receptor to recognize host cells, and the protease TMPRSS2 for priming the Spike protein, facilitating virus entry into cells. However, the involvement of estrogenic receptors in SARS-CoV-2 infection are still being explored. Thus, in order to investigate the role of estrogen and its receptors in COVID-19, the estrogen receptors ERα, ERβ and GPER1 were overexpressed in bronchial BEAS-2B cell, and then infected with SARS-CoV-2. Interestingly, the levels of ACE2 and TMPRSS2 mRNA were higher in SARS-CoV-2-infected cells, but no difference was observed in cells with estrogen receptors overexpression. GPER1 can be involved in virus infection or replication, since its higher levels reduces SARS-CoV-2 load. On the other hand, pharmacological antagonism of GPER1 enhanced viral load. Those data suggest that GPER1 has an important role in SARS-CoV-2 infection.

Keywords: BEAS-2B; COVID-19; Estrogen receptors; GPER1; Gender.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • COVID-19*
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Estrogens
  • Peptidyl-Dipeptidase A / metabolism
  • RNA, Messenger / genetics
  • Receptors, Estrogen
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / metabolism

Substances

  • Angiotensin-Converting Enzyme 2
  • Spike Glycoprotein, Coronavirus
  • Receptors, Estrogen
  • Estrogen Receptor beta
  • Estrogen Receptor alpha
  • Peptidyl-Dipeptidase A
  • RNA, Messenger
  • Estrogens
  • spike protein, SARS-CoV-2