A new target for the treatment of covid?
Mitochondrial proteins may become a new target for therapy of coronavirus infection
With a new coronavirus infection, the innate immune response, in which interferon proteins are involved, turns out to be much weaker than with other ARVI. Figuring out the mechanisms of this phenomenon, scientists have suggested that it's all about the interaction of the virus with mitochondria – the "power stations" of our cells.
Article by Miller et al. Host mitochondrial transcriptome response to SARS-CoV-2 in multiple cell models and clinical samples is published in the journal Scientific Reports.
Mitochondria are cellular organelles in which, due to the oxidation of nutrients, a high–energy compound (adenosine triphosphate, ATP) is synthesized, which serves as a universal source of energy for biochemical processes. At the same time, in mitochondria, as in real power plants, "waste" is formed – mainly reactive oxygen species (ROS).
For a long time it was believed that ROS are only a dangerous by-product that damages cellular structures and accelerates the aging process. But in recent decades, it has become clear that these compounds, including oxygen ions, free radicals and peroxides, play an important role in regulating various processes, including contributing to the development of an interferon antiviral immune response. So the good work of mitochondria provides one of the first lines of defense against viruses, including SARS-CoV-2.
Since it is known that coronavirus proteins are able to interact with mitochondria, it has been suggested that SARS-CoV-2 can alter the work of mitochondrial genes. After all, these cellular structures, which today occupy up to a quarter of the entire intracellular volume, have their own genome inherited from their ancestors – ancient bacteria who learned to use oxygen for energy production, which have become a kind of cellular "symbionts". However, most of the mitochondrial proteins are still encoded in the cell nucleus of modern cells.
Researchers from the University of Southern California (USA) the available data on RNA molecules "read" from the DNA of mitochondria, as well as from nuclear genes encoding mitochondrial proteins, were analyzed. These data were obtained as a result of the study of lung tissue samples and fluid taken during bronchoscopy from COVID-19 patients, as well as samples of cell cultures infected with SARS-CoV-2 or other viruses (respiratory syncytial, type A influenza, human parainfluenza).
It turned out that SARS-CoV-2 suppresses the work of nuclear DNA genes encoding mitochondrial proteins of complex I of the respiratory electron transport chain, which are necessary to maintain energy balance. This can generally reduce the "useful" work of mitochondria, including the production of ROS needed to fight the virus.
But the most important thing is that SARS-CoV-2 had almost no effect on the level of RNA molecules read from nuclear genes encoding the MAVS protein (Mitochondrial Antiviral Signaling). This protein, which is part of the mitochondrial membrane, serves as a kind of "signaling", informing the cell of a viral attack, and thus coordinates the work of the mitochondria and the interferon antiviral response. In the presence of other viruses, the activity of the MAVS gene and, accordingly, the concentration of this protein usually decreases, which causes an increased immune response.
However, when infected with SARS-CoV-2, this does not happen, and the immune response is weaker. Thus, MAVS represents a promising specific target for the development of therapeutic agents against COVID-19 and other coronavirus infections.
Portal "Eternal youth" http://vechnayamolodost.ru