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Source: Charite – Universitatsmedizin Berlin Natural variation influences virus-relevant proteins Representation of 179 human proteins and their relationship to SARS-CoV-2 or COVID-19 (Graphic: M. Pietzner). Joint press release by Charité – Universitätsmedizin Berlin and the Berlin Institute of Health (BIH) Like all viruses, the new coronavirus also depends on the help of the human host cell. The function carriers of the cell, the proteins, act as receptors to enable the virus to enter the host cell or to help it reproduce. Scientists from Charité – Universitätsmedizin Berlin and the Berlin Institute of Health (BIH) have now examined the corresponding genes of the helper proteins together with colleagues from Great Britain, Germany and the USA in a large study. In doing so, they came across a multitude of variants that influence the amount or function of the proteins and thus their ability to support the virus. They thus reveal possible target structures for new drugs. The researchers have now published their results in the journal Nature Communications. * Like any virus infection, an infection with the new SARS-CoV-2 coronavirus proceeds according to a specific scheme: First, the viruses bind to receptor proteins on the surface of the human body Host cells in the throat, nose or lungs, then they enter the cell, where they multiply with the help of the host cell machinery. The newly formed virus particles cause the infected cell to burst and infect other cells. As soon as the immune system notices what is happening, a defense mechanism is set in motion with the aim of destroying and removing both the virus and virus-infected cells. If everything goes as it should, the infection will usually be over after two weeks. For all these processes, however, the virus is dependent on proteins from humans or the host. “In severe COVID-19 courses, this regulated course has gotten out of control and the immune system causes an excessive inflammatory reaction that not only attacks virus-infected cells, but also healthy cells Tissue, “says Prof. Dr. Claudia Langenberg, BIH professor for Computational Medicine and head of the recently published study. “Naturally occurring variations of the genes that influence the blueprint for these human proteins can change their concentration or function and thus be a cause of the different course of the disease,” says Prof. Langenberg. The team is familiar with genetic variants that affect the concentration or structure of proteins and other molecules in human blood. “As molecular epidemiologists, we examine the diversity in the genes, i.e. the instructions for building proteins of entire population groups, in order to uncover susceptibility to diseases, the cause of which lies in the interplay of many small deviations,” explains the scientist, who was released by the Medical Research Council in September Epidemiology Unit at the University of Cambridge moved to BIH. “We now wanted to use these experiences and data sets for the COVID-19 epidemic and make them available to the scientific community.” “We have 179 proteins that were known to be involved in a SARS-CoV-2 infection, examined for their naturally occurring variants, ”reports Dr. Maik Pietzner, first author of the study and scientist with Prof. Langenberg in the laboratory. “We were already able to fall back on results that were based on samples from the first COVID-19 patients at the Charité.” This was made possible by the close collaboration with Prof. Dr. Markus Ralser, Director of the Institute for Biochemistry at the Charité, who was able to publish results on this before. Prof. Langenberg’s team was able to use data from a comprehensive population study, the MRC Fenland cohort, which contains information from more than 10,000 study participants. In doing so, they discovered 38 target structures for drugs that are already available as well as indications that certain proteins that interact with the virus also influence the immune system. “Our results also help to better understand risk factors for the sometimes severe courses of COVID-19, so we were able to show that blood coagulation proteins are influenced by the same genetic variant that also increases the risk of developing COVID-19 which causally determines blood group 0 “, reports Dr. Pietzner. The team immediately made the results publicly available on a web server that was developed with colleagues from Helmholtz Zentrum München (https://omicscience.org/apps/covidpgwas/). Since then, scientists all over the world have been using the data to identify target structures for new drugs or to better understand the course of COVID-19. “Even before our work was officially published, articles were published that use our findings,” says Prof. Langenberg happily. “That is exactly what we hoped for!” * Pietzner M et al. Genetic architecture of host proteins involved in SARS-CoV-2 infection. Nat Commun (2020), DOI: 10.1038 / s41467-020-19996z.

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LinksOriginal publicationCharité press release on COVID-19 biomarkers from June 4th

ContactProf. Dr. Claudia LangenbergCharité – Universitätsmedizin BerlinBIH – AG Computational Medicinet: +49 30 450 570 400

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