Otmar D. Wiestler
We want to help overcome the crisis with our top-level research. A significant part of our work is now focused on studying coronavirus.
We’re facing incredible challenges due to the COVID-19-pandemic, both as a society and as individuals. As Germany’s largest scientific organisation, Helmholtz is making key contributions to overcoming the coronavirus crisis through its top-level research.
Helmholtz experts are working at full speed to provide more research results on coronavirus. We are addressing one of the greatest challenges of our time in over 20 of our research projects – primarily in the field of health, but in other research fields as well. Helmholtz is dedicating part of its research to the new virus. Our researchers are working to decode the structure of the virus and its transmission routes as well as develop more effective medications and a vaccine.
Helmholtz has powerful, cutting-edge infrastructure in the field of biomedicine. Examples include drug screening capabilities as well as big data and AI applications that analyse molecular processes at the cellular level. We are using many of these structures to research SARS-CoV-2 and identify potential active substances.
Researchers at the Helmholtz Centre for Infection Research (HZI) are focusing on developing medications and vaccines to fight the virus and are working to unravel the mechanisms behind the pathogenesis and progression of the disease. For example, broad-spectrum active substances against SARS-CoV-2 are sought through screening. The HZI is establishing corresponding preclinical infection models for this purpose. Researchers at the HZI also use time-resolved single-cell RNA sequence analysis of patient samples to investigate virus-host interactions at different points in time of infection.
The German Cancer Research Center (DKFZ) has set up a task force with input from eleven departments and working groups. Their goal is to develop a vaccine as well as diagnostic methods. In addition, the task force is researching the mechanisms of how COVID-19 develops as a disease.
To identify new active substances against the virus, researchers at the German Center for Neurodegenerative Diseases (DZNE) are analysing the ACE2 virus receptor and the TMRPPS2 protease that allows the virus to fuse with cell membranes. The DZNE has also started to screen existing, commercially available drugs for their potential use as treatment options against SARS-CoV-2. Researchers here are conducting laboratory tests that allow high-precision single-cell analyses.
Viruses enter the cell by attaching to specific receptor proteins (lock and key principle). Researchers at Forschungszentrum Jülich are developing a molecule that specifically attaches to the same receptor and therefore competes with the virus. This can block the virus from penetrating the cells. The team at Jülich is also working to decode the 3D structure of another viral protein (ORF8) and conducting tests to determine how this protein can be inhibited. A third project is examining how a viral enzyme (a 3C-like protease) can be inhibited. The researchers already know that the virus needs this protein to replicate as well.
In addition, the Jülich Supercomputing Center is teaming up with its partners at the Gauss Centre for Supercomputing to provide computer resources so computer-assisted simulations can be carried out to assess the effect of potential drugs, for example.
At the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), researchers are using various methods including single-cell biology to analyse how lung cells respond to infection with the novel coronavirus compared to the old SARS-CoV-1 – both at the level of the mRNA of the body’s cells and the virus’s RNA as well as at the protein level. Other groups at MDC are examining the antibodies the body forms in response to COVID-19, and these teams of researchers are looking at ways of blocking the ACE2 receptor that the virus uses to penetrate the cells.
In order to develop vaccines using inactivated viruses, researchers need methods that kill off the virus while causing as little damage to its structure as possible – especially the viral envelope that’s key to the immune response. To strike this balance, researchers from HZI and the GSI Helmholtz Centre for Heavy Ion Research are using heavy ions rather than gamma rays to kill the virus. The heavy ions leave the viral envelope largely intact in comparison to conventional methods. Viruses that are destroyed using this method are then tested so new vaccines can be developed.
The GSI Helmholtz Centre for Heavy Ion Research together with international collaborators is working on the development of highly sensitive sensors based on nanopores to improve virus identification and to be able to detect infections with the SARS-CoV-2 virus faster. These sensors have the potential to detect viruses specifically and quickly. In another project, GSI plans to use these nanopores to develop safe mouth protection filters and thus improve breathing masks. With a diameter down to 10 to 20 nanometers, nanopores are significantly smaller than the corona virus SARS-CoV-2 and can therefore protect against virus infection.
In a preclinical study, GSI also plans to test whether pneumonia triggered by SARS-Cov-2 can be treated with low-dose radiation. The university hospitals in Frankfurt and Erlangen partner with the GSI for this study. For this purpose, the researchers are using a typical low-dose X-ray irradiation, as it has already been administered for the treatment of pneumonia, as well as whole-body exposure due to a slightly increased radon activity in the environment. The aim is to be able to treat pneumonia caused by SARS-CoV-2 more effectively in the future.
The Helmholtz Centre for Infection Research is also looking at the dynamics of how the infection is spreading among the population. Developed at HZI, the SORMAS app is dedicated to disease control and risk assessment processes and can now be put into use for the SARS-CoV-2 pandemic as well. This new coronavirus module makes it possible to detect individual cases of COVID-19 patients at an early stage even in remote regions, to document clinical details and laboratory confirmations, to accompany all contact persons and to be able to offer them therapy at an early stage – in case they also fall ill. At the same time, SORMAS generates data in real time for ongoing risk assessment at national and international level. SORMAS has been established in regions with weak infrastructure; now the HZI and the Robert Koch Institute are working on making the system available to German health authorities.
A further app-based software development PIA (Prospective Monitoring of Acute Infection Application) from the HZI is currently being introduced in order to record regular self-reports on the health status of important contact persons using mobile phones. It focuses on the monitoring of immunocompromised patients. In comparison with reference values from the general population, it will be determined whether there is a particular risk with regard to the frequency of infection or the course of the disease.
In order to detect antibodies in recovered COVID-19 patients, the HZI is developing tests for epidemiological studies to better track the viral disease and thus the possible acquired immunity against SARS-CoV-2. These tests help to determine the infection’s actual extent. In a population study coordinated by the HZI, the blood of more than 100,000 donors is also regularly analyzed for antibodies against the COVID-19 pathogen. These seroprevalence studies provide a more accurate picture of already acquired immunity and the further development of the pandemic. Together with the RKI, the HZI is investigating the actual spread of the virus in Germany in several large-scale studies in particularly affected areas.
In cooperation with the German Cancer Research Center (DKFZ) and the NMI Natural and Medical Sciences Institute at the University of Tübingen, the Helmholtz Centre for Infection Research is developing multiplex serological tests that represent a new diagnostic tool for measuring protective antibody reactions. These tests will generate high-resolution data to assess the specific serological prevalence of SARS-CoV-2 in comparison to other respiratory viruses, the duration of an immune response or the susceptibility to infection among study participants on a population level.
In addition, scientists at the HZI and the Forschungszentrum Jülich are simulating the effect of different conditions on the development of the SARS-CoV-2 epidemic in Germany. In order to describe the spread of the pathogen more precisely, the researchers have extended a classical model from mathematical epidemiology to include SARS-CoV-2-specific components. By integrating information on the number of patients admitted to hospital and undergoing intensive care into the model, they are able to predict the burden on the German healthcare system in different propagation scenarios. The modelling significantly contributed to the Helmholtz position paper on the epidemiological situation.
The Forschungszentrum Jülich makes its supercomputing capacities available at the Jülich Supercomputing Centre (JSC). The aim is to provide precise data on the virus’ spread and drug development as quickly as possible.
Together with other international research institutions and companies, the Research Center has joined the Canadian quantum computer manufacturer D-Wave Systems Inc.’s initiative to support researchers in developing solutions to combat the corona pandemic. D-Wave provides free access to quantum computer systems for users researching COVID-19. Partners from CINECA, Kyocera, NEC Solution Innovators Ltd., the QAR-Lab at LMU Munich, the University Tōhoku and Volkswagen, in addition to Forschungszentrum Jülich are helping to implement the project.
Together with the University of Heidelberg and the Frankfurt Institute for Advanced Studies (FIAS), the JSC is developing mathematical models of the dynamics of corona eruption in Germany, which can also be used to simulate the effect of containment measures. The goal is to predict when the outbreak will peak and how many people might become ill. In addition, the JSC and its partners at the Gauss Centre for Supercomputing (GCS) are providing computing time.
The EXSCALATE4CORONAVIRUS (E4C) project needs such computing time. The project involves a close collaboration among three of largest supercomputing centres in the EU - CINECA in Italy, the Barcelona supercomputing centre in Spain and the supercomputing centre of Forschungszentrum Jülich in Germany - along with a pharmaceutical company, and several universities and research Institutes. These include the Jülich Institute of Neuroscience and Medicine, Computational Biomedicine (INM-9). The E4C team use supercomputers to perform molecular simulations and in silico, i.e. using special programs or algorithms, biochemical and phenotypic screening of existing drugs against SARS-CoV-2. This approach allows the fast analysis of simulation results and reduces the time required to discover new therapeutic agents. Indeed, the EXSCALATE platform permits exascale virtual screening and therefore the evaluation of billions of molecules against several targets within few weeks.
Researchers at Helmholtz Zentrum München establish precision monitoring tools to guide societal restrictions and future vaccination strategies. They identify risk factors for SARS-CoV-2 infection and complications in Diabetes and Chronic Lung Disease patients. They are using KORA, NAKO cohorts and available biobanks from diabetes and chronic lung disease patient cohorts.
The Center for Disaster Management and Risk Reduction Technology (CEDIM) at Karlsruhe Institute of Technology (KIT) is teaming up with Risklayer GmbH, an analysis database that conducts risk assessments, to collect current data on the development of the coronavirus pandemic. The maps created by the team provide an overview of how the virus is spreading in Germany and around the world and also identify risk areas down to the district level.
Researchers at MDC have developed a new online tool (in German) that maps the progression of the COVID-19 epidemic in Germany as a whole as well as broken down by the individual federal states. The map and timeline showing the spread of coronavirus are accessible free of charge. The map and timeline now also show the case numbers for all countries worldwide.
Researchers have succeeded in using the high-intensity X-ray light of the BESSY II synchrotron radiation source at the Helmholtz-Zentrum Berlin (HZB) to decode the three-dimensional architecture of an enzyme. This is the main viral protease of SARS-CoV-2, which is involved in the reproduction of the virus. Analyzing this protein could help determine specific points of attack in the development of active substances. The researchers are now continuing their work at BESSY II and are using the fragment screening method developed there: They’re gradually testing different molecules until the best components for a suitable active substance are identified. From the results, it is possible to determine which fragments dock at the viral protease’s active center. These fragments can then be used as components of an active substance.
The Deutsches Elektronen-Synchrotron DESY has launched a series of trials that closely examine the three key proteins of the pathogen. If the analyses are successful, DESY’s work could significantly speed up the search for a drug to treat COVID-19.
The Centre for Structural Systems Biology (CSSB) at DESY is collaborating closely with all organisations working on infection research in northern Germany. Using “supermicroscopes” such as DESY’s PETRA III synchrotron radiation source and devices known as cryo-electron microscopes allows the researchers to examine biological specimens of various types. This extends from analyzing the structure of individual molecules to mapping processes in living cells in real time. PETRA III is on standby and can be started up at any time in order to conduct measurements relating to coronavirus. A fast-track access mode has been set up to this end. The team at DESY is putting together a number of research projects that are relevant to SARS-CoV-2. Examples include determining the structure of virus proteins and an X-ray fluorescence method that tracks how the virus spreads in tissues.
The Cancer Information Service at the German Cancer Research Center (DKFZ) and the Pulmonary Information Service at the Helmholtz Zentrum München (HMGU) have stepped up their capacities so they can respond to queries from people who may have a compromised immune system, including cancer patients or individuals with underlying medical conditions affecting the lungs, as well as their relatives. Information pages on the novel coronavirus and the COVID-19 lung disease caused by the virus have also been created. The Allergy Information Service offers further information about coronavirus for people with allergies and asthma (in German).
People with diabetes can obtain scientifically verified information relating to their questions on coronavirus on diabinfo, the diabetes information portal launched by the Helmholtz Zentrum München and its partners.
The European Commission has announced the funding of 17 new projects with a total volume of 47.5 million euros to help fight the coronavirus pandemic. All projects are international in scope and deal with monitoring, testing, treatment and vaccine development. The 17 projects were selected from 90 submitted applications. Helmholtz scientists coordinate two of these projects:
The Helmholtz Zentrum München, German Research Center for Environmental Health, coordinates RiPCoN ("Rapid interaction profiling of 2019 nCoV for network based deep drug repurpose learning"). Together with partners from France and Spain, the researchers will determine whether currently approved drugs are suitable for the treatment of COVID-19. The researchers initially hope to find out which proteins, signalling pathways and molecular structures the virus exploits and alters in the human body. On the basis of this information, they will model – supported by artificial intelligence and machine learning – which drugs have a chance of success and are promising for subsequent laboratory tests and studies. In the project’s second phase, they want to use experiments to find out what effects naturally occurring genetic differences of interacting human and viral proteins have on the individual course of the disease. Combined with further data on epidemics and human genes, these findings will be used for future COVID-19 risk management and resource planning of hospitals.
The Helmholtz Centre for Infection Research (HZI) coordinates CORESMA ("COVID-19 Outbreak Response combining E-health, Serolomics, Modelling, Artificial Intelligence and Implementation Research"). This project aims to close existing gaps between clinical, epidemiological and immunological information in order to better respond to the pandemic. European researchers from the Netherlands, Switzerland and Germany, as well as partners from China, Côte d'Ivoire and Nepal are working together to achieve this goal. They intend to obtain real-time clinical data via the SORMAS app developed by the HZI together with national and international partners since 2014, which will allow data on disease outbreaks to be recorded locally and transmitted to health authorities. The focus here is on particularly endangered countries, including Ivory Coast, Ghana and Nigeria. At the same time, investigations will be carried out in Germany and Nepal to determine whether infections with other human corona viruses lead to cross-immunity against the novel SARS-CoV-2. The data collected will help to better assess the transmission of the virus and to evaluate the effectiveness of measures against its spread.
The Helmholtz Centre for Infection Research is also involved in the SCORE project; Forschungszentrum Jülich is involved in the Exscalate4CoV project. "SCORE" is intended to develop antiviral drugs that can be used in the short to medium term to treat patients and contain the spread of coronaviruses. The "Exscalate" platform is already aiming to use supercomputing resources and link them with life science research laboratories in order to respond more quickly and efficiently to international pandemics. The project is now being expanded to include COVID-19; this also involves the identification of active substances against the virus.
The Alliance of Science Organisations is an association of the major non-university science organizations in Germany. The majority of the Helmholtz Association's alliance activities take place in close cooperation with the German Centres for Health Research (DZG). The German Centre for Infection Research (DZIF) plays a coordinating role.
The platform "Lean European Open Survey on SARS-CoV-2 Infected Patients" (LEOSS) established at DZIF is used by all DZG as a central IT platform for anonymized patient data.
In addition, central DZG-wide clinical studies are initiated, taking into account special risk groups (patients with lung or cardiovascular diseases, diabetes and cancer). The DZIF also coordinates German participation in international studies such as the WHO Solidarity Trial.
In addition to these overarching measures, the DZG provides infrastructure for clinical studies, substance libraries for testing SARS-CoV-2 and expertise in medicinal chemistry and good manufacturing practice (GMP).
In more than 20 research projects Helmholtz is addressing one of the greatest challenges of our time.