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

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Costa, Angelica Jardim ; Lemes, Robertha Mariana Rodrigues ; Bartolomeo, Cynthia Silva ; Nunes, Tamires Alves ; Pereira, Gabriela Cruz ; Oliveira, Rafaela Brito ; Gomes, Alexandre Lopes ; Smaili, Soraya Soubhi ; Maciel, Rui Monteiro de Barros ; Newson, Louise ; Ramirez, Ana Lopez ; Okuda, Liria Hiromi ; Prado, Carla Maximo ; Stilhano, Roberta Sessa ; Ureshino, Rodrigo Portes

• Document type: Journal article
• Source: Molecular and Cellular Endocrinology; v. 558, p. 8-pg., 2022-12-01.

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 ER alpha, ER beta 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. (AU)

• FAPESP's process: 20/04709-8 - Evaluation of potential therapeutically compounds for SARS-CoV-2: focus on estrogen-related compounds, autophagy modulators and ACE2
• Grantee: Rodrigo Portes Ureshino
• Support Opportunities: Regular Research Grants
• FAPESP's process: 06/60402-1 - Medular carcinoma of the thyroid: revisiting the clinical, molecular biological, biochemical and biological aspects following findings of molecular genetics
• Grantee: Rui Monteiro de Barros Maciel
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/06088-0 - Effects of eugenol and dehidrodieugenol isolated from Nectandra leucantha (Lauraceae) treatments in experimental models of acute and chronic lung disease
• Grantee: Carla Máximo Prado
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/13480-4 - Virtual screening and in vitro and in vivo evaluation of nicotinic receptors as a therapeutic target for SARS-CoV-2: focus on interaction with ACE2.
• Grantee: Carla Máximo Prado
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/06153-7 - Evaluation of estrogen-related compounds and autophagy modulators seeking for therapeutic targets against SARS-CoV-2
• Grantee: Robertha Mariana Rodrigues Lemes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/02762-9 - Evaluation of estrogen-mediated neuroprotection in cellular model of the tauopathy
• Grantee: Rafaela Brito Oliveira
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 16/20796-2 - Study of estrogen receptors mediated autophagy against tau toxicity in cell and zebrafish models
• Grantee: Rodrigo Portes Ureshino
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 19/10922-9 - Gene and cell therapy via alginate microgels for muscle injuries
• Grantee: Roberta Sessa Stilhano Yamaguchi
• Support Opportunities: Research Grants - Young Investigators Grants