A NEW complex mechanism of action by which the coronavirus damages us has just been identified: infected cells are pushed to “suicide”, to death – in technical jargon apoptosis – by the virus itself. This was revealed by a research group from the University of Hong Kong that conducted tests on animals and human cells grown in the laboratory with the Mers-Cov virus, very similar to Sars-Cov-2, the cause of the Mers epidemic in 2012. and 2013. To these are added the first tests based on the new coronavirus.
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The results, just published in Science Advances, are still quite preliminary; however, they open a path of research, for the future, of new therapeutic options against Covid-19: a path, that of the study of new therapies, which must never be abandoned, even now that we have vaccines.
Coronavirus and the genes that drive cells to death
The researchers investigated mice and human lung tissue grown in the laboratory. As mentioned, the virus used is not Sars-Cov-2 but “resembles” it, since it belongs to the same family and is one of the coronaviruses capable of infecting humans. Scientists examined the behavior of bronchial epithelial cells 12 and 24 hours after they were infected with Mers-Cov – in particular they studied mRna transcription sequences. From the examination it emerged that some genes involved in the phenomenon of cell death were very present or better, always in technical jargon, “very expressed”. Test results show that the virus can push cells to self-annihilate in a programmed death. It is a self-defense action that serves the cells themselves to find escape from the virus, but which at the same time damages them irreparably.
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“This reaction – he comments Andrea Cossarizza, Professor of General Pathology and Immunology at the University of Modena and Reggio Emilia – has been extensively studied for decades for many other pathologies, and for example it has already been demonstrated for some influenza viruses. “Cell death, continues the expert, can involve a large number of cells, including those important for the correct functioning of various organs. “We know – adds Cossarizza – that apoptosis is a defense mechanism of the organism that in this way eliminates infected cells, capable of producing and spreading pathogenic. But at the same time this is also one of the mechanisms by which a virus can damage the organism. Therefore open a further avenue of research and identify the molecular mechanisms activated by a coronavirus such as Mers-Cov, as happened in this first study , it may be important to better understand the activity of this and other coronaviruses “.
The road to new treatments for Covid
In addition, the researchers investigated how to act to counter cell death. The physiological mechanism is very complex: the genes associated with cell death are in turn regulated by other components, in particular by the so-called “signaling path” of the Perk protein – a sort of biological network or pathway that activates and sees the participation of many members. “This path – underlines Cossarizza – is widely studied by scientists to counteract apoptosis in other pathologies as well. The study in question reveals that the coronavirus analyzed, Mers-Cov, also acts by activating this particular molecular pathway, whose action can be associated with apoptosis both in the animal model and in human cells “.
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The authors then observed that by using molecules that inhibit Perk (and therefore called Perk inhibitors), thus blocking this path, it is possible to obtain results to prevent apoptosis. In this way, with Perk inhibitors, a “substantial improvement” is observed in the tissues grown in the laboratory, as they write in the text in Science Advances, “both with respect to apoptosis induced by the Mers-Cov virus, and with respect to the spread of the virus from a cell “. The findings are to be taken with caution, as they concern cell studies and the Mers-Cov coronavirus.
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In the coronavirus Sars-Cov-2, the cause of Covid-19, the mechanisms that lead to cell death are somewhat different, and for this reason, as the study shows, Perk inhibitors are not effective in fighting apoptosis. However, early evidence in mice with Sars-Cov-2 seems to indicate that another inhibitor, a different molecule, could also limit cell death and reduce damage to lungs and other tissues.
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