The researchers’ finding opens the door to new treatments against the disease
Scientists from the UMU and the IMIB deciphered the effects of a key protein in Covid-19, called ‘spike’ or spicule in Spanish, through which the virus accesses the body and which has been used by RNA vaccines to help activate the immune system. The scientific journal Science Advances has just published the results of the research, the results of which could determine which treatments would be the most appropriate to curb the inflammation it causes in the body and the associated symptoms in the different variants.
The ‘Immunity, Inflammation and Cancer’ team, led by Victoriano Mulero Méndez, together with the IMIB research group led by Mª Luisa Cayuela Fuentes ‘Temolerase, Cancer and Aging’, developed a zebrafish model, chosen for its genetic similarity with the human being and its transparency, which makes it possible to study the effects of the ‘spike’ protein and its interaction with the immune system when it comes to fighting infections.
The leading role of ‘spike’
When SARS-CoV-2 infects our body and accesses cells, it does so precisely through this protein. Spike binds to the ACE2 protein that coats the cell surface, acting like a key fits a lock, letting the virus through.
“Vaccines based on messenger RNA, that is, Pfizer and Moderna, as well as Astra Zeneca, which uses adenovirus technology, precisely induce the production of this protein so that our body learns to recognize it and generates an army of soldiers, the lymphocytes. , that they attack it quickly in the face of an infection, ”explains the UMU researcher Victoriano Mulero. Therefore, knowing how it interacts with the immune system can be of great relevance to better understand the mechanism of action of these vaccines and to develop new antiviral therapies to treat the disease. “Until now there are few therapies and they have not been shown to be effective, so we must continue working in this field,” concludes Mulero.
The results reveal that when the virus enters this protein induces a strong inflammation, due to the great production of cytokines, as well as neutrophils and macrophages; the two types of cells of the immune system that respond to the virus most quickly. “Precisely, the use of inflammasome inhibitors is suggested in patients with more severe Covid-19 to reduce inflammation and the number of neutrophils and macrophages, which can end up leading to a syndrome known as a cytokine storm, which is responsible for the deterioration of the patient and that can cause his death, “says Cayuela. “Cytokines, in their correct proportion, would be a kind of ‘immunity hormones’ that regulate the response to infections, but if they are produced in excess they damage the body”, explains the researcher.
Similar results have been obtained by treating zebrafish with the angiotensin 1-7 molecule, which is precisely what produces the cell surface protein (ACE2) through which the virus gains access. Previous research has suggested that the virus reduces the amount of angiotensin 1-7 in the body, an alteration that would further accentuate inflammation. In this sense, the researchers are considering using this molecule as a treatment to prevent the so-called cytokine storms from occurring.
Other results
The UMU researchers have also been able to verify that spike causes hemorrhages, another of the adverse effects of SARS-CoV-2 infection, and that it had not been possible to reveal to date due to the scarcity of animal models to study this disease. . In this sense, treatment with angiotensin 1-7 could be used at the same time to reduce bleeding, further supporting its possible therapeutic use in COVID-19.
Finally, one of the most novel results is that the protein acts on each of the variants with very different effects. Thus, for example, in Delta it is much less inflammatory than the original variant. This result could explain why it is more contagious, “since it would allow it to multiply in the patient without being detected by the immune system and without producing symptoms, which would also facilitate its transmission by asymptomatic people,” concludes Mulero.
This work has been made possible thanks to funding from a project by the Seneca Foundation, whose main author was Sylwia Tyrkalska and in which scientists Alicia Martínez López, Ana Belén Arroyo Rodríguez, Francisco Javier Martínez Morcillo, Sergio Candel Camacho, Pablo Mesa del Castillo, and Diana García Moreno.
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