They identify several drugs potentially capable of reducing the mortality of Covid-19


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Researchers of the
National Cancer Research Center (CNIO)
, present in an article published in
Scientific Reports
a lList of drugs that could deal with Covid-19. due to its immunosuppressive potential.

In addition, their work suggests that the higher mortality from Covid-19 in men could be due to anti-inflammatory properties of female hormones.

Inflammation is a defense of the body to fight against pathogens. However, when it occurs in an excessive and generalized way, it can aggravate the pathology and even cause death. One of the ways this over-response occurs is known as cytokine storm, an inflammatory process produced by these proteins, the cytokines, which send a signal to the immune system to activate.

“This response is what frequently kills those affected by SARS-CoV-2 and not so much the virus itself,” explains Óscar Fernández-Capetillo, from the CNIO.

The study also identifies drugs that could potentially aggravate the severity of the cytokine storm, and that would therefore be contraindicated in Covid-19 patients.

Although respiratory failure associated with Acute Respiratory Distress Syndrome (ARDS, for its acronym in English) is the main cause of mortality from Covid-19, an accumulation of evidence shows that lethality in a subgroup of seriously ill patients occurs due to the late onset of an inflammatory cytokine storm, points out Article.

In order to find “antidotes”, the researchers used the incipient scientific studies that emerged from April 2020 and that identified the changes in gene expression of the lung cells of SARS-CoV-2 patients who died of a cytokine storm. These data were used to interrogate the database Connectivity Map, developed by the Broad Institute, belonging to
WITH
and the
Harvard University,
It contains the changes in gene expression that induce nearly 5,000 compounds, including all drugs approved for clinical use.

Fernandez-Capetillo.
Fernandez-Capetillo. – CNIO

The objective was to identify potential “antidotes”, compounds that induce changes in the expression of genes opposite to those observed in Covid-19 patients. “The study predicts that glucocorticoids such as dexamethasone they should be effective in combating mortality in Covid-19 patients, which was comforting since, in fact, these drugs are, among others, the ones used in hospitals to combat death from Covid-19″, he points out. Fernandez-Capetillo.

The results suggest that the higher mortality from Covid-19 in men could be due to the anti-inflammatory properties of female hormones.

To their surprise, the researchers identified – and subsequently validated in vitro – that MEK protein inhibitors, commonly used in cancer treatments, had a strong anti-inflammatory effect.

The researchers emphasize that, in any case, any therapy based on anti-inflammatory drugs -including glucocorticoids- should be restricted to the late and severe phases of Covid-19, since the use of anti-inflammatory therapies in early phases of the disease would limit the effectiveness of the immune system in its fight against infection.

Another noteworthy aspect is that all the analyzes of the study converge in indicating that female hormones could combat the cytokine storm, which could contribute to understanding why men suffer a greater severity of the pathology.

“Also, it would be consistent with the fact that the difference in mortality by sex is mitigated at advanced ages, when the menopause and estrogen levels decline», explains Fernández-Capetillo.

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