Estrogen Receptor Modulators in Viral Infections Such as SARS-CoV-2: Therapeutic Consequences

Int J Mol Sci. 2021 Jun 18;22(12):6551. doi: 10.3390/ijms22126551.


COVID-19 is a pandemic respiratory disease caused by the SARS-CoV-2 coronavirus. The worldwide epidemiologic data showed higher mortality in males compared to females, suggesting a hypothesis about the protective effect of estrogens against severe disease progression with the ultimate end being patient's death. This article summarizes the current knowledge regarding the potential effect of estrogens and other modulators of estrogen receptors on COVID-19. While estrogen receptor activation shows complex effects on the patient's organism, such as an influence on the cardiovascular/pulmonary/immune system which includes lower production of cytokines responsible for the cytokine storm, the receptor-independent effects directly inhibits viral replication. Furthermore, it inhibits the interaction of IL-6 with its receptor complex. Interestingly, in addition to natural hormones, phytestrogens and even synthetic molecules are able to interact with the estrogen receptor and exhibit some anti-COVID-19 activity. From this point of view, estrogen receptor modulators have the potential to be included in the anti-COVID-19 therapeutic arsenal.

Keywords: COVID-19; IL-6; SARS−CoV−2; cytokine storm; estrogen; estrogen receptor; viral replication.

Publication types

  • Review

MeSH terms

  • Breast Neoplasms / complications
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • COVID-19 / complications
  • COVID-19 / pathology*
  • COVID-19 / virology
  • Estrogen Receptor Modulators / metabolism
  • Estrogen Receptor Modulators / pharmacology*
  • Estrogen Receptor Modulators / therapeutic use
  • Female
  • Humans
  • Receptors, Estrogen / chemistry
  • Receptors, Estrogen / metabolism
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / physiology
  • Viral Matrix Proteins / antagonists & inhibitors
  • Viral Matrix Proteins / metabolism
  • Virus Internalization / drug effects
  • Virus Replication / drug effects


  • Estrogen Receptor Modulators
  • Receptors, Estrogen
  • Viral Matrix Proteins
  • membrane protein, SARS-CoV-2