Drugs with the capacity to curb the mortality of COVID-19 are identified

Researchers at the National Cancer Research Center (CNIO) have made a hierarchical list of compounds capable of curbing the body’s inflammatory response, which could help reduce mortality in the most seriously ill patients with COVID-19 and in patients with other pathologies in which intervenes the inflammatory phenomenon.

Inflammation is a response of the body to fight pathogens but sometimes it is excessive and generalized and can aggravate a pathology and even cause death.

This excessive response is known as a ‘cytokine storm’ and is caused by proteins of the same name (cytokines), which send a signal to the immune system to activate.

In fact, “this response is what frequently kills those affected by SARS-CoV-2 and not so much the virus itself”, recalls Óscar Fernández-Capetillo, head of the CNIO Genomic Instability Group and main author of the list published today in the journal Scientific Reports.

The list includes all the compounds capable of stopping this chemical storm that, in the most serious cases of COVID-19, causes respiratory failure associated with Acute Respiratory Distress Syndrome, the main cause of death of COVID-19 promoted by a storm of cytokines.

In order to find “antidotes”, the researchers used the scientific studies that emerged from April 2020 and that identified the gene expression changes of the lung cells of SARS-CoV-2 patients who died from a cytokine storm.

This premise served to search the Connectivity Map database, from the Broad Institute (a research center of MIT and Harvard University), which contains changes in gene expression that induce nearly 5,000 compounds, including all approved drugs. for clinical use.

The objective was to identify compounds capable of inducing changes in the expression of genes opposite to those observed in COVID-19 patients.

“The study predicts that glucocorticoids such as dexamethasone should be effective in combating mortality in COVID-19 patients″, which are some of the drugs used in hospitals to combat death from COVID-19, Fernández-Capetillo highlights.

The authors also identified that MEK protein inhibitors, which are used in cancer treatments, have a strong anti-inflammatory effect.

In this sense, they warn that any therapy based on anti-inflammatory drugs -including glucocorticoids- should be limited to the late and severe phases of COVID-19, since the use of anti-inflammatory therapies at the beginning of the disease can limit the effectiveness of the immune system. in its fight against infection.

The study also found that female hormones could combat the cytokine storm, which could contribute to understanding why men suffer from greater severity of the pathology and “It would be consistent with the fact that the difference in mortality by sex is mitigated at advanced ages, when menopause already appears and estrogen levels decrease”, explains Fernández-Capetillo.

The work, which gives a panoramic view of drugs with the potential to combat the cytokine storm, was put in a public repository at the end of 2020 and “practically all the molecules that we predicted at the time have been validated in later work by other groups”, indicates the researcher.

Finally, the list identifies drugs that could potentially aggravate the severity of the cytokine storm and that, therefore, would be contraindicated in COVID-19 patients.

The study has been possible, to a large extent, thanks to the work of Laura Sánchez-Burgos, from the CNIO Bioinformatics Unit, who, “During the hardest part of the confinement in Madrid, he resorted to computational approaches to be able, from home, to be of help and investigate relevant problems associated with SARS-CoV-2″, highlights Fernández-Capetillo.