Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

SARS-CoV-2 and the Possible Connection to ERs, ACE2 and RAGE: Focus on Susceptibility Factors

Version 1 : Received: 9 May 2020 / Approved: 10 May 2020 / Online: 10 May 2020 (17:46:13 CEST)

A peer-reviewed article of this Preprint also exists.

Stilhano, R.S.; Costa, A.J.; Nishino, M.S.; Shams, S.; Bartolomeo, C.S.; Breithaupt‐Faloppa, A.C.; Silva, E.A.; Ramirez, A.L.; Prado, C.M.; Ureshino, R.P. SARS‐CoV‐2 and the Possible Connection to ERs, ACE2, and RAGE: Focus on Susceptibility Factors. The FASEB Journal 2020, 34, 14103–14119, doi:10.1096/fj.202001394rr. Stilhano, R.S.; Costa, A.J.; Nishino, M.S.; Shams, S.; Bartolomeo, C.S.; Breithaupt‐Faloppa, A.C.; Silva, E.A.; Ramirez, A.L.; Prado, C.M.; Ureshino, R.P. SARS‐CoV‐2 and the Possible Connection to ERs, ACE2, and RAGE: Focus on Susceptibility Factors. The FASEB Journal 2020, 34, 14103–14119, doi:10.1096/fj.202001394rr.

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 pre-existing 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 symptomology, 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.

Keywords

COVID-19; estrogen; RAGE; ACE2

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

Comments (2)

Comment 1
Received: 10 May 2020
Commenter: MARIA RITA DE ASSIS
The commenter has declared there is no conflict of interests.
Comment: Muito instrutivo e coerente. Revela notável conhecimento do tema. Parabéns
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Response 1 to Comment 1
Received: 13 May 2020
The commenter has declared there is no conflict of interests.
Comment: I am glad that you liked the review. Thanks!
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