17β‐estradiol reduces SARS‐CoV‐2 infection in vitro

Lemes, Robertha Mariana Rodrigues; Costa, Angélica Jardim; Bartolomeo, Cynthia Silva; Bassani, Taysa Bervian; Nishino, Michelle Sayuri; Pereira, Gustavo José da Silva; Smaili, Soraya Soubhi; Maciel, Rui M. B.; Braconi, Carla Torres; Cruz, Edgar Ferreira da; López, Ana; Maricatto, Juliana Terzi; Janini, Luiz Mário; Prado, Carla M.; Stilhano, Roberta Sessa; Ureshino, Rodrigo Portes

doi:10.14814/phy2.14707

Cited by 49 publications

(72 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As the sterols can potentially modify virus infection capacity, pretreatment with estrogen is likely to enhance protective actions in acute lung injury due to the anti-inflammatory effects. 63 A previous study suggested that estrogen could lower the activities of CMI, HI, and innate immune cells, like neutrophils and NK cells.…”

Section: Estrogenmentioning

confidence: 98%

Immunological aspects and gender bias during respiratory viral infections including novel Coronavirus disease‐19 (COVID‐19): A scoping review

Vadakedath

Kandi

Mohapatra³

et al. 2021

Journal of Medical Virology

View full text Add to dashboard Cite

The human immune system is not adequately equipped to eliminate new microbes and could result in serious damage on first exposure. This is primarily attributed to the exaggerated immune response (inflammatory disease), which may prove detrimental to the host, as evidenced by SARS‐CoV‐2 infection. From the experiences of Novel Coronavirus Disease‐19 to date, male patients are likely to suffer from high‐intensity inflammation and disease severity than the female population. Hormones are considered the significant pillars of sex differences responsible for the discrepancy in immune response exhibited by males and females. Females appear to be better equipped to counter invading respiratory viral pathogens, including the novel SARS‐CoV‐2, than males. It can be hypothesized that females are more shielded from disease severity, probably owing to the diverse action/influence of estrogen and other sex hormones on both cellular (thymus‐derived T lymphocytes) and humoral immunity (antibodies).

show abstract

Section: Estrogenmentioning

confidence: 98%

Immunological aspects and gender bias during respiratory viral infections including novel Coronavirus disease‐19 (COVID‐19): A scoping review

Vadakedath

Kandi

Mohapatra³

et al. 2021

Journal of Medical Virology

View full text Add to dashboard Cite

show abstract

“…We emphasize that we tested the effects of 4-OHT and fulvestrant at their therapeutic concentrations and demonstrated that they can signi cantly in uence the susceptibility of human ER expressing MCF7 cells to SARS-CoV-2 infection. Our results envision a therapeutic use of tamoxifen in infected people to restrain the severity of the symptoms, COVID-19 mortality and the vicious circle induced by SARS-CoV-2 infection on ACE2 and TMPRSS2 expression [47]. Potentially also a prophylactic use could reduce the risk of infection and spread of the disease.…”

Section: Discussionmentioning

confidence: 87%

Tamoxifen protects breast cancer patients from COVID-19: first evidence from real world data

Bravaccini

Nicolini

Balzi

et al. 2021

Preprint

View full text Add to dashboard Cite

Background COVID-19 severity is uneven between genders. We hypothesized a role of hormonal therapies in the severity of COVID-19 in breast cancer (BC) patients via the modulation of SARS-CoV-2 susceptibility genes. Patients and Methods We mined the Emilia Romagna region (Italy) registries to compare the rates of hospitalization and mortality for COVID-19 in 2020 amongst 24628 BC patients. Next, we analyzed the modulation of ACE2, TMPRSS2 and NRP1 gene expression and the susceptibility to SARS-CoV-2 infection by tamoxifen, fulvestrant and 17β-estradiol on human ER+ MCF-7 cells in vitro.Results The hospitalization rate observed for 4784 tamoxifen treated BC patients was the lowest (OR, 0.41; 95% CI, 0.18-0.94; p=0.04) among hormonal therapies and no fatalities occurred. A standard mortality rate reduction has been observed also for patients treated with aromatase inhibitors (SMR: 0.73; 95% CI, 0.45-0.90). In vitro experiments showed that fulvestrant, but not tamoxifen, increases ACE2, TMPRSS2 and NRP1 gene expression and susceptibility to SARS-CoV-2 infection and that 17β-estradiol reduces significantly TMPRSS2 and NRP1 expression.Conclusions Tamoxifen treated BC patients showed a reduced rate of hospitalization and strikingly no fatalities for COVID-19. In vitro experiments confirmed a protective role of tamoxifen while an increased susceptibility to SARS-CoV-2 infection of ER+ cells treated with fulvestrant was observed.

show abstract

“…These mechanisms were also dependent on the interaction of hormones with their receptors. The inhibitory effect of estrogens on replication was documented [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ]. in a panel of viruses (for particulars see Table 1 ).…”

Section: Effect Of Oestrogen Receptor Modulators (Erms) On Viral Replicationmentioning

confidence: 99%

“…Unfortunately, the precise molecular mechanisms of action were deciphered only in a few cases and are usually independent of the interaction with the receptor. Clomifene, raloxifene, ridaifene (+XL-147) and toremifene act via attenuation of the interaction of SARS−CoV−2 or EBOLA with their target cells [ 37 , 40 , 41 , 42 , 43 , 44 ], where some role of the inhibition of SARS−CoV−2 spike protein interaction with receptor ACE2 may be expected [ 36 , 37 , 39 , 44 , 45 , 67 ]. ERMs seem to inhibit the glycan–glycan interaction between the spike protein and ACE2 and so reduces the virus entry to permissive cells [ 43 , 68 ].…”

Section: Effect Of Oestrogen Receptor Modulators (Erms) On Viral Replicationmentioning

confidence: 99%

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

Abramenko

Vellieux

Tesařová

et al. 2021

IJMS

View full text Add to dashboard Cite

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.

show abstract

17β‐estradiol reduces SARS‐CoV‐2 infection in vitro

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 49 publications

References 31 publications

Immunological aspects and gender bias during respiratory viral infections including novel Coronavirus disease‐19 (COVID‐19): A scoping review

Immunological aspects and gender bias during respiratory viral infections including novel Coronavirus disease‐19 (COVID‐19): A scoping review

Tamoxifen protects breast cancer patients from COVID-19: first evidence from real world data

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

Contact Info

Product

Resources

About