The DZIF focuses on SARS-CoV-2 research
Up-to-date information
Last update: 05.08.2021
Scientists and doctors at the German Center for Infection Research (DZIF) are working at full speed to put together a research package that pursues ambitious goals. New diagnostic testing methods, antiviral drugs and a vaccine against the new SARS coronavirus are on the agenda. Additional funding has been made available through fast track procedures. The DZIF is initiating research projects and coordinating clinical trials together with the other German Centers for Health Research.
„We are optimistic that our research work at the DZIF can make substantial contributions in the fight against the virus.“
Prevention: Vaccine development
DZIF scientists in München, Marburg and Hamburg are developing a vector vaccine based on genetic information of a SARS-CoV-2 surface protein which is inserted into a vector. Two vectors are being developed in parallel: A modified smallpox virus which has been rendered harmless (MVA) and the measles virus.
Research status: 1,000 single doses of the MVA vector vaccine were produced by IDT Biologika for the clinical trial phase. The clinical trials in humans started at the beginning of October 2020. In phase I, tolerability and the stimulation of immune responses were tested. For further development, the scientists are cooperating with the companies IDT Biologika (Dessau) and CanVirex (Basel) for the measle vaccine.
Results of the Phase I clinical trial showed that the vaccines are safe and well tolerated - however, the immune responses were below expectations. The phase II trial planned for early 2021 was therefore postponed. With an optimised vaccine, phase I has been continued since mid-July 2021.
Healthy volunteers between the ages of 18 and 64 who have not yet been vaccinated against SARS-CoV-2 nor have contracted SARS-CoV-2 in the past are still being sought for the study: The study includes a health screening, two vaccination appointments and 14 control appointments within a period of seven months. The volunteers will receive an expense allowance. Those interested in participating in the study can contact the medical contracting institute CTC North:
email
Telefon: +49 40 524719 111
www.ctc-north.com
Press release on the MVA vector vaccine - 16.07.2021
Press release on the measles virus vaccine - 01.12.2020
Treatment: Emergency drugs
Despite the availability of vaccines, the development of antiviral drugs against COVID-19 is still important in order to be able to help those with severe courses of the disease. In vitro assays and animal models created in the process of vaccine development now also serve as a basis for testing antiviral substances. Especially agents which have already been approved for other indications hold promise as drugs which could be used in the short term. The DZIF is involved in developing different agents:
Developing specific inhibitors of the main protease in Sars-CoV-2
Prof. Rolf Hilgenfeld and his team at the University of Lübeck succeeded in elucidating the main protease’s precise structure, and consequently develops a first inhibitor termed RHCDS-13b into a drug.
Inhibitor of the cellular enzyme TMPRSS2
Infection biologists from the German Primate Center - Leibniz Institute for Primate Research in Göttingen, together with DZIF colleagues at Charité Universitätsmedizin Berlin, have investigated how the novel coronavirus SARS-CoV-2 penetrates cells. They have identified a cellular enzyme that is essential for viral entry into lung cells: the protease TMPRSS2. A clinically proven drug known to be active against TMPRSS2, Camostat Mesilate, was found to block SARS-CoV-2 infection and might constitute a novel treatment option.
Neutralising antibodies for prevention and treatment of COVID-19
A team of researchers led by Prof. Florian Klein (Cologne University Hospital) and the German Center for Infection Research (DZIF) has isolated potent SARS-CoV-2 neutralizing antibodies. They have great potential to be used for prevention and treatment of the infection. Together with the University of Marburg and the company Boehringer Ingelheim, a highly potent antibody is currently being tested in a clinical trial.
Researchers rely on known substances
MHH professor and DZIF scientist Thomas Pietschmann leads the German part of an international consortium of scientists. This research network is searching for substances that act against SARS-CoV-2 in the world's largest substance repurposing bank "ReFrame".
Understanding the virus
Dr. Alexander Simonis, assistant physician and second author of the study, Dr. Sebastian Theobald, postdoc and first author of the study and DZIF scientist Priv.-Doz. Dr. Jan Rybniker, Head of the Infectious Diseases Research Laboratory and last author of the study (from left to right).
Why do some people get seriously ill with COVID-19?
After infection with SARS-CoV-2, some infected individuals respond with an exaggerated immune response to the virus. Severe inflammation of the lungs and other organs can be the result. Researchers at the University Hospital of Cologne and the German Center for Infection Research (DZIF) are investigating the effect of the viral spike protein on the innate immune system, which is strongly associated with severity of disease. The research team has been able to show that certain white blood cells (macrophages, also known as phagocytes) are massively stimulated by the viral spike protein to produce the pro-inflammatory signalling molecule interleukin 1. Macrophages belong primarily to the innate immune system, which is distinguished from the acquired immune system.
The Coronavirus attacks human cells and forces the host cells to form new virus components like nucleotides, proteins and fatty acids. A computer model identified the human guanylat kinase as a possible target for different virus mutants.
How a computer model visualises the weaknesses of SARS-CoV-2
For more than a year, the group around Tübingen’s DZIF scientist Andreas Dräger has worked on a computer model that identifies weaknesses of the virus and, thus, potential attack points. Previously, the researchers have already identified a human enzyme as such a promising target. Their latest study confirms this result. Furthermore, the bioinformaticians show new attack points and demonstrate that they also apply to the new mutants.
The SUD protein of SARS coronavirus (orange) forms a complex with the human protein Paip-1 (cyan). The elements of the two proteins that interact particularly strongly are colored green (SUD) and purple (Paip-1).
How does SARS-CoV-2 trick the human cell?
DZIF scientists Prof. Rolf Hilgenfeld and Dr Albrecht von Brunn discovered how SARS viruses enhance the production of viral proteins in infected cells, so that many new copies of the virus can be generated. Other coronaviruses apart from SARS-CoV and SARS-CoV-2 do not use this mechanism, thereby providing a possible explanation for the much higher pathogenicity of the SARS viruses. When comparing the RNA genomes of coronaviruses harmless for man and that of the SARS coronavirus, researchers identified a region that only occurred in the latter and was hence called "SARS-unique domain" (SUD).
A mass spectrometer device (detail): Using mass spectrometric analysis at the Max Planck Institute of Biochemistry, the researchers discovered 1484 interactions between viral and human cellular proteins.
What happens when SARS-CoV-2 infects a cell?
What exactly happens when the corona virus SARS-CoV-2 infects a cell? In an article published in Nature, a team from the Technical University of Munich (TUM) and the Max Planck Institute of Biochemistry and paints a comprehensive picture of the viral infection process. For the first time, the interaction between the coronavirus and a cell is documented at five distinct proteomics levels during viral infection. This knowledge will help to gain a better understanding of the virus and find potential starting points for therapies. More than 1,200 samples were analyzed using the state-of-the-art mass spectrometry techniques and advanced bioinformatic methods. The result is a freely accessible dataset that provides information on which cellular proteins the viral proteins bind to and the effects of these interactions on the cell.
Clinical trials
The German Center for Infection Research participates in the coordination of research on COVID-19 vaccines.
How protective is a COVID-19 combination vaccine?
Up until now, there were no data available to indicate to what extent the human organism would react to a combined vaccination from AstraZeneca and an mRNA vaccine and start to form antibodies. A team of researchers, among others of the DZIF, has now proven that the antibody response is much stronger with the combination vaccine than with two doses of the AstraZeneca vaccine. The immune response to combination vaccines has proven to be just as good as the antibody response after two vaccinations with the mRNA vaccine from BioNTech/Pfizer.
When SARS-CoV-2 (yellow) infects monkey kidney cells, it reduces the cellular recycling mechanism, meaning there are fewer autophagy signals (green) than in non-infected cells. Blue staining depicts nuclei.
A tapeworm drug against SARS-CoV-2?
Researchers from the German Center for Infection Research (DZIF) at Charité – Universitätsmedizin Berlin and the University of Bonn were able to identify four substances which inhibit SARS-CoV-2 replication in the host cell. The most pronounced antiviral effect was associated with niclosamide, which the researchers had shown to be effective against the MERS coronavirus during an earlier study. A phase II trial will test the safety, tolerability, and efficacy of niclosamide combined with camostat (another licenced drug) in patients recently diagnosed with COVID-19. Anyone interested in participating in the study can obtain more information from the Charité Research Organisation at +49 30 450 539 210 or patienten@charite-research.org.
The team of researchers determined the viral load for more than 25,000 COVID-19 patients.
Who is most contagious?
What started as a preliminary evaluation of laboratory data in 2020 has since evolved into the largest-ever investigation of viral load levels in patients with SARS-CoV-2. A team of researchers from the German Center for Infection Research and Charité – Universitätsmedizin Berlin have now analyzed the PCR samples of more than 25,000 persons with COVID-19. Working under the leadership of Prof. Dr. Christian Drosten, the team determined the viral loads of each individual sample and used their results to estimate levels of infectiousness. No notable differences in viral load levels were recorded among SARS-CoV-2-positive individuals aged between 20 and 65 years. Viral loads were found to be lowest in very young children (0 to 5 years).
A central participant registry for COVID-19 vaccine studies is now being created at the German Center for Infection Research.
Would you like to participate in a COVID-19 vaccine trial in Germany?
A central participant registry is created at the German Center for Infection Research (DZIF); those interested can register there. Supported by the German Ministry of Education and Research (BMBF), the DZIF Clinical Trial Unit at the University Hospital Cologne is setting up a platform across Germany and Europe that provides an overview of experienced clinical trial sites for testing vaccines against the new coronavirus.
Further information and registering
Study register for SARS-CoV-2 and COVID-19
In order to attain an overview of all clinical trials taking place in Germany and to provide an effective network for the researchers, the Clinical Trial Unit of the DZIF at Cologne University has, for the first time, created a registry for all clinical trial activities taking place in Germany - involving now SARS-CoV-2/COVID 19. For the first time, not only DZIF study activities are presented here: In order to provide a comprehensive overview in the current pandemic situation of planned and already active COVID-19 studies in Germany, the Clinical Trial Unit is cooperating with researchers from various German Centers for Health Research and other networks.
To the overview of ongoing clinical studies
The German Center for Infection Research participates in the coordination of research on COVID-19 vaccines.
Research network VACCELERATE
The need for vaccine studies continues to be high, as many questions remain unanswered about the safety, efficacy and possibly necessary adaptation of vaccines to emerging virus variants. In order to coordinate these studies, the European Union is funding the creation of the new VACCELERATE vaccine research network. To date, 26 partner institutions from 21 European countries are participating in the network. VACCELERATE will be the pandemic preparedness network that will establish a structure for the quick and effective development and testing of vaccine candidates across Europe, also beyond Corona.
LEOSS – a European registry
The DZIF and the German Society of Infectious Diseases (DGI) have set up a European case registry which is to collect clinical data of patients with SARS-CoV-2 infection. A special feature of this new registry is that all the data collected will be made available to the scientific community for use in joint analyses. LEOSS is multilingual and is to be implemented across the entire EU. By mid-January 21, 6000 patient data had already been recorded.
The "LEOSS.sero-suvey" platform - gaining insight into immunity in the population
Following the example of the LEOSS case registry, which has been collecting and evaluating clinical data of COVID-19 patients throughout Europe since March 2020, the German Center for Infection Research is now establishing the "LEOSS.sero-survey" platform. This platform allows for the timely comparison and cross-analysis of different antibody studies on immunity or seroprevalence in the population. The project is led by scientists at the Helmholtz Centre for Infection Research (HZI) and is implemented in cooperation with the Helmholtz Federated IT Services (HIFIS).
Diagnosis: Rapid and safe tests
Coronaviruses (colored transmission electron microscopy image).
Shortly after the outbreak in China in January 2020, DZIF scientists at Charité – Universitätsmedizin Berlin developed the first test for SARS-CoV-2. Using the virus’s genetic information, Prof. Christian Drosten and his team succeeded in developing a test based on the PCR (polymerase chain reaction) technique. The test is currently being used worldwide. Now the aim is to refine the test methods as well as to develop and validate new tests which can be used to determine immune responses in the human body. “We will only be able to develop a vaccine once we know what happens inside the patient’s body,” Drosten explains.
International cooperation
New coalition for resource-pour countries
A group of scientists, physicians, funders, and policy makers from over 70 institutions from over 30 countries have launched an international coalition to respond to COVID-19 in resource-poor settings. DZIF was the first organization in Germany to join the coalition.The COVID-19 Clinical Research Coalition aims to accelerate desperately needed COVID-19 research in those resource-poor settings.
Interesting links on the topic
Federal Ministry of Education and Research: information portal on the coronavirus
Word Health Organization (WHO)