TY - JOUR
T1 - SARS-CoV-2 and the possible connection to ERs, ACE2, and RAGE
T2 - Focus on susceptibility factors
AU - Stilhano, Roberta Sessa
AU - Costa, Angelica Jardim
AU - Nishino, Michelle Sayuri
AU - Shams, Shahin
AU - Bartolomeo, Cynthia Silva
AU - Breithaupt-Faloppa, Ana Cristina
AU - Silva, Eduardo Alexandre
AU - Ramirez, Ana Lopez
AU - Prado, Carla Maximo
AU - Ureshino, Rodrigo Portes
N1 - Funding Information:
The authors thank to the Funda??o de Amparo ? Pesquisa do Estado de S?o Paulo?FAPESP: 2016/20796-2 (RPU), 2020/04709-8 (RPU), 2018/16719-8 (MSN), 2018/06088-0 (CMP); Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior?CAPES: code 001 (AJC, CSB), Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico?CNPq: 303035/2018-8 (CMP); FAP-FCMSCSP 2019/2021; NIGMS-funded Pharmacology Training Program: T32GM099608 (SS); American Heart Association grant number 19IPLOI34760654 (EAS).
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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.
AB - 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.
KW - ACE2
KW - COVID-19
KW - estrogen
KW - RAGE
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UR - http://www.scopus.com/inward/citedby.url?scp=85091298249&partnerID=8YFLogxK
U2 - 10.1096/fj.202001394RR
DO - 10.1096/fj.202001394RR
M3 - Review article
C2 - 32965736
AN - SCOPUS:85091298249
VL - 34
SP - 14103
EP - 14119
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 11
ER -