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

Nikita Abramenko,Daniel Rösel,Robert Kaplánek,Lukáš Lacina,Zdeněk Kejík,Fréderic Vellieux,Adam Tesař,Petra Tesařová,Barbora Dvořánková,Jan Brábek,Karel Smetana,Milan Jakubek

doi:10.3390/ijms22126551

Abstract

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.

Highlights

COVID-19 is a severe respiratory infection that possesses a pandemic character caused by the SARS−CoV−2 coronavirus, which is a virus similar to the SARS and MERS viruses.Published global epidemiologic data show that while the incidence of infection is only negligibly sex-dependent with some protective role of estrogens in premenopausal women, males die more frequently than females [1,2]
Experimental data obtained from ovariectomized mice showed more severe courses of SARS−CoV or MERS infections than in control animals [3], which supports the hypothesis that estrogens possess a certain protective effect against viral infection in females because of their anti-inflammatory and immunomodulatory effect [4]
This observation is supported by an independent study performed in Peru, where male COVID-19 patients with androgenic alopecia suffer from severe COVID-19 more frequently than infected males who do not suffer from this type of alopecia [13]

Summary

Introduction

COVID-19 is a severe respiratory infection that possesses a pandemic character caused by the SARS−CoV−2 coronavirus, which is a virus similar to the SARS and MERS viruses. Experimental data obtained from ovariectomized mice showed more severe courses of SARS−CoV or MERS infections than in control animals [3], which supports the hypothesis that estrogens possess a certain protective effect against viral infection in females because of their anti-inflammatory and immunomodulatory effect [4]. Chidataobserved concerning the rolepremenopausal of estrogens are and equivocal because there are no signese women [5]. This can be due to the high dietary intake of isoflavonoids in Eastern nese women [5]. Eastern nificant differences in mortality observed between premenopausal and postmenopausal Asia.

Number

Physiological Estrogen Receptor-Dependent Effects and Viral

Antiviral Effect of Estrogens as a Developmental Strategy

Therapeutic Consequences

Procedures of of Molecular