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Influenza drug prevents SARS-CoV-2 from invading host cells - Innovation Origins

International scientists have discovered that aprotinin can prevent the SARS-CoV-2 virus from entering host cells.

The corona pandemic is still raging around the globe. And it is still causing record numbers of infections and disease-related deaths on a daily basis. At the same time, there are new glimmers of hope almost every day that this state of emergency will come to an end in the foreseeable future. The development of vaccines is making leaps and bounds. Biontech/Pfizer,Moderna, and now also AstraZeneca are close to obtaining approval for their products. But there is also a constant stream of new insights when it comes to drugs for treating COVID-19, the disease caused by the coronavirus. Scientists at the Goethe-Universität Frankfurt am Main in Germany, the University of Kent (UK), and the Medizinische Hochschule Hannover (Germany) have now discovered that the protease inhibitoraprotinin can prevent cells from becoming infected. In the past, aprotinin was used to treat post-operative bleeding. Nowadays, doctors in Russia use it to treat influenza. Spikes become inactive The SARS-CoV-2 virus is covered in spike proteins on its surface. It uses these spikes to dock to proteins (ACE2 receptors) on the surface of host cells. However, before this can be done, parts of the spike protein must be separated by the enzymes of the host cells – proteases. Under the supervision of Prof. Jindrich Cinatl, Institute of Medical Virology at Frankfurt University Hospital, and Prof. Martin Michaelis and Dr. Mark Wess (both from the University of Kent), researchers have now been able to demonstrate in experiments with different cell cultures that aprotinin can stop virus replication in the cells. The scientists explain that since SARS-CoV-2 reduces the formation of protease inhibitors by the host cells after infection, aprotinin is apparently able to compensate for this. The virus can no longer penetrate the host cells. Our findings show that aprotinin is effective against SARS-CoV2 in concentrations that can be achieved in patients, Professor Jindrich Cinatl “In aprotinin we have a drug candidate for the treatment of COVID-19 that is already approved for other indications and could readily be tested in patients. In Russia, aprotinin aerosols for the treatment of influenza have already been approved, given that these types of influenza viruses also need host cell proteases in order to penetrate cells.

Overly robust immune response can lead to critical cases of COVID-19 - Innovation Origins

A new study has shown that the body's very strong immune response to the SARS CoV-2 virus can cause a severe case of COVID-19.

The body’s immune system primarily fights viruses through antibodies and T lymphocytes (aka T cells). The antibodies bind to specific viral receptors and thereby prevent viruses from penetrating cells. At the same time, infected cells are tagged so that other protagonists in the immune system can then destroy the cell. Virus-specific T cells, on the other hand, are able to destroy infected cells directly. In studies carried out during the past few weeks, these cell-killing SARS-Cov-2–specific T cells were identified in patients who had gotten sick with COVID-19, triggered by the novel coronavirus. The results have revealed that these types of cells were mainly found in people who had survived a COVID-19 infection. “This suggests that these cells have a protective antiviral effect,” the scientists explain. On the other hand, some trials suggest that an overly robust immune response might be the cause of severe COVID-19 conditions. However, the role of SARS -Cov-2-specific T-cells in this overreaction is still unclear. Strength of the immune response is decisive Contrary to previous assumptions, the dreaded respiratory failure does not occur in critical cases of COVID-19 because the immune response is too weak. Quite the opposite. It seems that an immune system that responds too robustly may contribute to this type of respiratory failure. Researchers at the Marien-Hospital in Herne and the virology department at the Ruhr University Bochum (RUB, Germany) and the Clinics of Infectiology and Anaesthesia and the Institute of Virology at the Universitätsmedizin Essen (also Germany) have carried out extensive research on this topic. Under the direction of Prof. Dr. Nina Babel, head of the Center for Translational Medicine at the RUB Marien-Hospital Herne, the scientists have examined specific antibodies and T-cells in the disease progression of COVID-19 in patients suffering from a mild form, in patients who are critically ill, and in patients who subsequently died. They found that the immune responses were similar. In the study, which was published in the journal Cell Reports Medicine, the researchers analyzed the immune responses in patients with COVID-19. “We wanted to study the role of T-cells and antibodies in controlling infection and disease,” Nina Babel says. “The novelty of our study is that we have analyzed SARS COVID-2 specific T cells and antibodies with regard to disease progression and virus eradication. We found that a strong T cell and antibody response was not only detectable in patients with a mild case of COVID-19, or who had overcome the viral infection.” Patients who were critically ill and those who had experienced COVID-19-induced respiratory failure were found to have a comparable or even stronger immunity to SARS-Cov-2. Further research is needed “The number of specific immune cells, as well as their functional capacity, was no better in patients who survived COVID-19 than in those who died of the disease,” says Dr. Ulrik Stervbo, laboratory manager at the Center for Translational Medicine. There was also no difference in the robustness and functionality of the immune response between patients with persisting SARS-Cov-2 infections and those who had recovered. “Although further studies are needed in order to understand the specific mechanism of COVID-19-associated respiratory failure, our data suggest that an excessive SARS-Cov-2-specific T-cell immune response triggers immunopathogenesis. This consequently causes life-threatening critical conditions,” says Nina Babel, lead researcher. “The results of the ongoing studies on the successful application of immunosuppressive therapies for COVID-19 support this hypothesis”, summarises Prof. Dr. Timm Westhoff, Director of the Medical Clinic I of the Marien-Hospital Herne. The original publication:Constantin J. Thieme, Moritz Anft et al.: A robust T cell immunity towards spike, membrane, and nucleocapsid SARS-CoV-2 proteins is not associated with recovery in critical COVID-19 patients, in: Cell Reports Medicine, 2020, DOI: 10.1016/j.xcrm.2020.100092: https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(20)30118-X

A new process for precision perforation of material layers - Innovation Origins

A nano-structuring method for precisely perforating one layer of material while leaving the other layer completely untouched

Scientists at the Vienna University of Technology (TU Wien) in Austria have succeeded in a new feat: They have developed a method that allows them to perforate certain layers of material precisely while leaving others completely untouched. Is it just art? No, this could be interesting for the production of data storage devices. It’s actually pretty obvious: You can’t shoot a bullet through a banana, perforate the skin and leave the banana undamaged. But at the level of ultra-thin atomic layers this is now possible, as recently proven by scientists at the Vienna University of Technology (TU Wien). They developed a nano-structuring method with which they can precisely perforate one layer of material while leaving the other layer completely untouched, even though the “projectile” penetrates all layers. This is made possible with the help of highly charged ions. They can be used to selectively process the surfaces of novel, ultra-thin 2D material systems. In this way, certain metals, which then serve as catalysts, can be anchored on them. “We investigated a combination of graphene and molybdenum disulphide,” says Dr. Janine Schwestka from the Institute of Applied Physics at the Vienna University of Technology and lead author of the current publication, describing the new feat. “The two layers of material are brought into contact and then adhere to each other by weak van der Waals forces. Ultra-thin layers To understand this, you have to know that materials that are composed of several ultra-thin layers are regarded as a great area of hope in materials research. Ever since the high-performance material graphene – which consists of only a single layer of carbon atoms – was first produced, new thin-film materials have been developed again and again. And these often have promising new properties. What’s more, for certain applications, the geometry of the material on a scale of nanometers needs to be specifically processed, for example, to change the chemical properties by adding additional types of atoms or to control the optical properties of the surface. “There are different methods for this,” explains Janine Schwestka. “You can change the surfaces with an electron beam or with a conventional ion beam. With a two-layer system, however, you always have the problem that the beam changes both layers at the same time, even if you actually only want to process one of them. Two kinds of energy When a surface is treated with an ion beam, the force of the impact of the ions normally changes the material. At the Vienna University of Technology, however, relatively slow ions were used, but were electrically charged several times. “You have to differentiate between two different forms of energy here,” explains Prof. Richard Wilhelm, who was awarded the FWF’s START Prize in 2019 for building the world’s first ultrafast ion source. “On the one hand, there is kinetic energy, which depends on the speed at which the ions strike the surface. On the other hand, there is potential energy, which is determined by the electric charge of the ions. With conventional methods, the kinetic energy was decisive, but for us the potential energy is particularly important. The essential difference is that while the kinetic energy is released in both layers of material when penetrating the layer system, the potential energy can be distributed very unevenly among the layers. “The molybdenum disulfide reacts very strongly to the highly charged ions,” says Richard Wilhelm. “A single ion arriving at this layer can remove dozens or hundreds of atoms from the layer. What remains is a hole, which can be seen very clearly under an electron microscope.” The graphene layer, on the other hand, which the projectile hits immediately afterwards, remains intact, since most of the potential energy has already been released. New data storage devices conceivable Schwestka also describes possible areas of application. “Graphene is a very good conductor, molybdenum disulfide is a semiconductor, and the combination could be interesting for the manufacture of new types of data storage devices, for example.” Incidentally, the same experiment can also be reversed, so that the highly charged ion first hits the graphene and then the molybdenum disulfide layer. In this case, both layers remain intact: The graphene provides the ion with the electrons it needs to neutralize it electrically in a tiny fraction of a second. The mobility of the electrons in the graphene is so high that the point of impact also “cools down” immediately. The ion traverses the graphene layer without leaving a permanent trace. Afterwards, it can no longer cause much damage in the molybdenum disulphide layer. “This provides us with a wonderful new method of manipulating surfaces in a targeted manner,” says Richard Wilhelm. “We can add nano-pores to the surface without damaging the substrate material underneath. This way we can create geometric structures that were previously impossible.” In this way, one could create “masks” from molybdenum disulfide perforated exactly as desired, on which certain metal atoms are then deposited exactly in the holes. This opens up completely new possibilities for controlling the chemical, electronic and optical properties of the surface. The new method was recently published in the technical journal “ACS Nano.”

Paradigm shift in the use of animal experiments: Fewer animals, more reliable results - Innovation Origins

Each year, around three million animals suffer and die in research laboratories worldwide. According to figures from the German Animal Welfare Federation, a total of 2,825,066 vertebrates and cephalop