SARS-CoV-2 and the possible connection to ERs, ACE2, and RAGE: Focus on susceptibility factors

Author(s)

Stilhano, Roberta Sessa ^[1] ; Costa, Angelica Jardim ^[2] ; Nishino, Michelle Sayuri ^{[3, 4]} ; Shams, Shahin ^[5] ; Bartolomeo, Cynthia Silva ^{[6, 1]} ; Breithaupt-Faloppa, Ana Cristina ^[7] ; Silva, Eduardo Alexandre ^[5] ; Ramirez, Ana Lopez ^[8] ; Prado, Carla Maximo ^[6] ; Ureshino, Rodrigo Portes ^{[3, 4]}

Affiliation

^[1] Fac Ciencias Med Santa Casa Sao Paulo, Dept Physiol Sci, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Pharmacol, Escola Paulista Med, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Biol Sci, Diadema - Brazil

^[4] Univ Fed Sao Paulo, Lab Mol & Translat Endocrinol, Escola Paulista Med, 781 Pedro Toledo St, BR-04039032 Sao Paulo, SP - Brazil

^[5] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 - USA

^[6] Univ Fed Sao Paulo, Dept Biosci, Santos, SP - Brazil

^[7] Univ Sao Paulo, Fac Med, Lab Cirurgia Cardiovasc & Fisiopatol Circulacao L, Inst Coracao InCor, Sao Paulo - Brazil

^[8] Cambridge Inst Med Res, Cambridge - England

• Document type: Review article
• Source: FASEB JOURNAL; v. 34, n. 11, p. 14103-14119, NOV 2020.
• Web of Science Citations: 3

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has provoked major stresses on the health-care systems of several countries, and caused the death of more than a quarter of a million people globally, mainly in the elderly population with preexisting pathologies. Previous studies with coronavirus (SARS-CoV) point to gender differences in infection and disease progression with increased susceptibility in male patients, indicating that estrogens may be associated with physiological protection against the coronavirus. Therefore, the objectives of this work are threefold. First, we aim to summarize the SARS-CoV-2 infection pathway and the roles both the virus and patient play in COVID-19 (Coronavirus disease 2019) progression, clinical symptomatology, and mortality. Second, we detail the effect estrogen has on viral infection and host infection response, including its role in both the regulation of key viral receptor expression and the mediation of inflammatory activity. Finally, we describe how ERs (estrogen receptors) and RAGE (receptor for advanced glycation end-products) play a critical role in metabolic pathways, which we envisage could maintain a close interplay with SARS-CoV and COVID-19 mortality rates, despite a current lack of research directly determining how. Taken together, we present the current state of the field regarding SARS-CoV-2 research and illuminate where research is needed to better define the role both estrogen and metabolic comorbidities have in the COVID-19 disease state, which can be key in screening potential therapeutic options as the search for effective treatments continue. (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: 18/16719-8 - The role of estrogen receptors in autophagy in cellular model of Tauopathy
• Grantee: Michelle Sayuri Nishino
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• 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: 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