There is no clear predominance of men or women in individuals diagnosed globally with new coronavirus. However, the majority of those who are hospitalized or die, that is, who develop the disease more severely, are men. According to the organization Global Health 50/50, maintained by University College London (United Kingdom), “in most countries, available data indicate that men are 50% more likely to die after diagnosis than women”.
This statement is corroborated by updated statistics from the city of New York, we United States, and by study carried out at China, according to which: “male gender is a risk factor for worse outcome in patients with covid-19, regardless of age and susceptibility”.
Based on this epidemiological finding, as well as on literature data, a large multidisciplinary team of researchers from the State of São Paulo is investigating the role of estrogens, female hormones, in the physiological protection against coronavirus.
The project Evaluation of compounds with therapeutic potential for SARS-CoV-2: focus on compounds with estrogenic activity, autophagy modulators and ECA2, coordinated by Rodrigo Portes Ureshino, professor at Federal University of São Paulo (Unifesp), is supported by FAPESP within the scope of the public notice Supplements for Rapid Implementation against covid-19.
“Previous studies, performed with the SARS-CoV coronavirus [causador da síndrome respiratória aguda grave], pointed out gender differences in infection and disease progression, with greater susceptibility of males, and indicated that estrogens could be associated with greater physiological protection for women. We want to test whether the same occurs with SARS-CoV-2, the new coronavirus, to arrive at compounds with therapeutic potential, ”says Ureshino to FAPESP Agency.
The team has already passed the literature review stage and entered the experimental phase itself. “We infected cell lines with wild strains of coronavirus and we will test in this model more than 40 compounds with estrogenic activity to observe the results”, says the researcher.
The procedures with SARS-CoV-2 are performed in a biosafety level 3 laboratory (NB3) at Unifesp, coordinated by professor Mário Janini, a project collaborator.
Among the compounds to be tested, Ureshino highlights 17ß-estradiol (the most abundant estrogen in the body), tamoxifen (a selective modulator of estrogenic receptors) and agenistein (a phytoestrogen). All three have already been used successfully in models of other viral diseases.
In addition to the strictly therapeutic focus, with the testing of compounds with the potential to treat covid-19, the project also has a molecular focus. In this case, the objective is to investigate the expression of the ACE-2 receptor (angiotensin-converting enzyme 2, in the acronym in English), which allows the virus to enter cells. “We know that hypertensive patients, a group at risk for covid-19, have a higher expression of ACE-2 and this favors the entry of the virus into cells. For this reason, we are studying the overexpression of this receptor in different cell types ”, says the researcher.
In this context, a pre-print article was produced by the group, with Dr. Roberta Sessa Stilhano, professor at the Faculty of Medical Sciences of Santa Casa (FCMSCSP) as its first author: “SARS-CoV-2 and the Possible Connection to ERs, ACE2 and RAGE: Focus onSusceptibility Factors “.
The work had the collaboration of Professor Carla Máximo Prado, from Unifesp, who studies the pulmonary inflammatory process, in addition to researchers from international institutions, such as the University of California – Davis (United States) and the University of Cambridge (United Kingdom).
“This article sought to correlate three factors: ACE-2, estrogen receptors and inflammation. So, in addition to the molecular pathways of ACE-2 and estrogens, we also detail the pathways of RAGE [receptor para produtos finais de glicação avançada], which is related to inflammation. We believe that the study of these pathways opens therapeutic perspectives for the treatment of covid-19 ”, says Stilhano.
In addition to the Unifesp team, the project has the collaboration of researchers from Faculty of Medicine, University of São Paulo (FM-USP) Ana Cristina Breithaupt-Faloppa and Luiz Felipe Pinho Moreira.