When it is widespread and excessive, it can aggravate the pathology and even cause death. Their usage might also be extended to other pathologies in which this inflammatory phenomenon also takes place.
In addition to forecasting drugs that might combat the cytokine storm, the paper likewise reports compounds that might possibly intensify this pathology. As might be expected, this list consists of drugs that either activate the immune system or improve inflammation. In addition, it exposes possible interactions with some oncology treatments or with the insulin signaling pathway.
In order to discover “antidotes,” the scientists utilized the incipient clinical studies that emerged from April 2020 onwards and identified changes in gene expression in lung cells from SARS-CoV-2 clients passing away as the outcome of a cytokine storm. These data were then utilized to probe the Connectivity Map database, developed by the Broad Institute, part of MIT and Harvard University, which consists of modifications in gene expression induced by around 5,000 compounds, including all drugs approved for medical usage.
CNIO researcher Óscar Fernández-Capetillo. Credit: CNIO
Cancer treatments as possible remedies versus SARS-CoV-2
The objective was to identify prospective “remedies,” substances that induce opposing modifications in the expression of genes to those seen in clients with COVID-19. “The research study anticipates that glucocorticoids such as dexamethasone must be efficient in combating death in clients with COVID-19, which was comforting due to the fact that, in reality, these drugs, in addition to others, are already being used in medical facilities to fight death from COVID-19,” states Fernández-Capetillo.
To their surprise, the researchers recognized– and consequently confirmed in vitro– that MEK protein inhibitors, commonly utilized in cancer treatments, had a strong anti-inflammatory impact. “I believe this anti-inflammatory home of MEK inhibitors is fairly unknown, and there needs to be more understanding about it because it increases our arsenal of anti-inflammatory compounds that could add to mitigating cytokine storms that can happen in a number of contexts, such as after transplants, chemotherapy, and other contagious illness including COVID-19,” states the biochemist.
The scientists stress that, in any case, any anti-inflammatory drug-based treatment– consisting of glucocorticoids– ought to be limited to the late and severe phases of COVID-19, since the use of anti-inflammatory therapies in the early stages of the illness would limit the efficiency of the immune system in its battle against infection.
Another essential aspect is that all the analyses conducted as part of the study assembled to indicate that female hormones could help to combat the cytokine storm, which might describe why males tend to get more severe types of COVID. “Also, it would follow the fact that the difference in death by sex is alleviated in innovative ages, when menopause appears and estrogen levels reduce,” describes Fernández-Capetillo.
The work, which uses a scenic overview of the drugs understood and readily available with the potential to fight the cytokine storm, was placed in a public repository at the end of 2020, “with the aim of making understanding readily available to as many individuals as possible,” while the paper was being evaluated. “Virtually all the particles we predicted at the time have actually been confirmed in later work by other groups, which is rewarding,” says the researcher.
In addition to anticipating drugs that might fight the cytokine storm, the paper also reports compounds that might possibly exacerbate this pathology. As may be anticipated, this list consists of drugs that either activate the immune system or enhance swelling. However, in addition, it reveals possible interactions with some oncology treatments or with the insulin signaling pathway.
With the assistance of the CNIO Bioinformatics Unit, the study “has been mostly the result of the perseverance and work of Laura Sánchez-Burgos, a student who, during the hard lockdown in Madrid, turned to computational approximations so that, although she was at house, she could be useful and investigate pertinent issues associated with SARS-CoV-2,” states Fernández-Capetillo.
In any case, as the authors clarify in the text of the article itself, the objective of this study is not to propose particular clinical indications for any of these representatives, but simply to make a contribution, in the context of the present health crisis, by providing concepts about drugs that could assist fight mortality in patients with COVID-19, and which other groups might check experimentally in preclinical models of the disease.
Recommendation: “An in silico analysis determines drugs possibly modulating the cytokine storm triggered by SARS‑CoV‑2 infection” by Laura Sanchez-Burgos, Gonzalo Gómez-López, Fátima Al-Shahrour and Oscar Fernandez-Capetillo, 31 January 2022, Scientific Reports.DOI: 10.1038/ s41598-022-05597-x.
Artistic imaginative illustration of a Cytokine Storm.
These particles would act by limiting the intensity of among the primary complications of the disease: the hyperreaction of the body immune system referred to as the cytokine storm, which is definitive in the most severe cases.
Swelling is a defense reaction of the body to combat pathogens. However, when it is extreme and widespread, it can aggravate the pathology and even cause death. Among the ways in which this extreme response happens is called a cytokine storm, an inflammatory procedure produced by these proteins, cytokines, which send out a signal that activates the immune system. “This reaction is frequently the cause of death in those impacted by SARS-CoV-2 rather than the virus itself,” explains Óscar Fernández-Capetillo, head of the Genomic Instability Group at the National Cancer Research Centre ( CNIO). He is among the authors of the short article released today in Scientific Reports, which sets out a hierarchical list of substances that could potentially help decrease death in the most major COVID clients, based on their power to stop this chemical storm. Their use might likewise be reached other pathologies in which this inflammatory phenomenon also happens.
Breathing failure associated with Acute Respiratory Distress Syndrome (ARDS) is the leading cause of death from COVID-19, a build-up of evidence reveals that lethality in a subgroup of severe patients takes place due to the late appearance of an inflammatory cytokine storm, the paper notes.
