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

• Main Authors: Nikita Abramenko, Fréderic Vellieux, Petra Tesařová, Zdeněk Kejík, Robert Kaplánek, Lukáš Lacina, Barbora Dvořánková, Daniel Rösel, Jan Brábek, Adam Tesař, Milan Jakubek, Karel Smetana
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: International Journal of Molecular Sciences
• Subjects: COVID-19; SARS−CoV−2; estrogen; estrogen receptor; viral replication; IL-6
• Online Access: https://www.mdpi.com/1422-0067/22/12/6551
• ISSN: 1661-6596; 1422-0067

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.