Drug discovery against SARS-CoV-2 and COVID-19

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Research on active substances against SARS-CoV-2 and COVID-19 aims to mitigate the course of the disease or prevent an outbreak. To this end, researchers are working on chemical substances that block the virus and on so-called neutralizing antibodies. These antibodies are isolated from recovered COVID-19 infected persons and could protect other people from infection for a limited period of time by means of a passive immunization.

Initiative to accelerate the development of therapies for COVID-19 and future coronavirus outbreaks

The new consortium CARE (Corona Accelerated R&D in Europe), funded by the public-private "Innovative Medicines Initiative" (IMI), announced its launch. The consortium aims to accelerate research and development of urgently needed drugs for the treatment of SARS-CoV-2, the virus that triggers COVID 19. CARE is supported with a total of €77.7 million in financial contributions from the European Union (EU) as well as financial and in-kind contributions from eleven companies of the European Federation of Pharmaceutical Industries and Associations (EFPIA) and three IMI-associated partners. CARE is designed to run for five years and brings together the work of 37 partner institutions from Belgium, China, Denmark, France, Germany, Great Britain, the Netherlands, Poland, Switzerland, Spain and the USA and is managed by VRI-Inserm (the French national institute for health and medical research in Paris, France), Janssen Pharmaceutica NV, one of the Janssen pharmaceutical companies of Johnson & Johnson (Beerse, Belgium), and Takeda Pharmaceuticals International AG (Zurich, Switzerland). CARE combines COVID-19 projects started by the partners since February 2020.

Contact:   Dr. Katharina Rox

Partners:

  • Helmholtz Center for Infection Research (HZI)
  • all 37 partners are listed on the website of the EU 

Funding: 77.700.000 € from the European Union (EU) and industrial partners

more information: Website of the HZI and Boehringer Ingelheim

Broad-spectrum agent against SARS-CoV-2

RESIST scientist Professor Pietschmann is leading the German research efforts of an international consortium that is looking for a drug against the coronavirus SARS-CoV-2 in the leading agent collection worldwide.


Innovation based on well-established agents, new indications for tried and true remedies – the principle of repurposing has often been successful in medicine. Therefore, it is also used against SARS-CoV-2: In order to quickly find a medication against COVID-19, an international research network is looking for a substance that is effective against SARS-CoV-2 in the world’s biggest drug repurposing bank “ReFrame”. The collection contains about 14.000 approved medications and agents with extensive data on safe human use. Multiple laboratories in the US, four in Great Britain, one in China and one in Germany are participating in the search. “ReFrame” was established in 2018 by Scripps Research (California) with support from the Bill and Melinda Gates Foundation.

Contact:   Prof. Dr. Thomas Pietschmann

Partners:

  • Charité - Universitätsmedizin Berlin
  • German Center for Infection Research (DZIF)
  • Helmholtz Institute for Pharmaceutical Research Saarland (HIPS)
  • Helmholtz Center for Infection Research (HZI)
  • Hannover Medical School (MHH)
  • Scripps University
  • TWINCORE – Centre for Experimental and Clinical Infection Research
  • University Bern

Funding: 1.071.000 € from the Lower Saxony Ministry of Science and Culture
 

More information: Websites of the TWINCORE and RESIST

InnoCoV – automation technologies in medical research

As a pioneer in applied research, the Fraunhofer-Gesellschaft is bringing together the expertise of 23 Fraunhofer institutions to develop new development and production technologies for innovative cell and gene therapeutics, as well as vaccines, in the “Production for Intelligent Medicine” innovation cluster.

The most recent case of the COVID19 pandemic once again has shown the tremendous challenges which arise in the context of the development and subsequent production of specific vaccines to respond to novel health risks. To help contain the pandemic, researchers of the Fraunhofer ITEM division of Pharmaceutical Biotechnology have designed a completely new production strategy for a coronavirus vaccine, which shortens the process development time for the production of investigational medicinal products for clinical trials down to a few months – in contrast to the usual 1.5 to 2 years.

In addition, Fraunhofer ITEM is bringing in its comprehensive know-how on the biology, production, and differentiation of stem cells and on lung macrophages. Within this project, quality characteristics and risk profiles will be developed for these cell types and then be used as a basis for automated production processes.

Contact:   Prof. Dr. Holger Ziehr

Partners:

  • Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM)
  • 23 other Fraunhofer Institutes

more information: Website of the ITEM

DRECOR: Using drug repurposing to develop drugs for inhalation therapy

The current global health emergency, triggered by the SARS-CoV-2 pandemic, urgently requires vaccines for prevention and drugs to cope with the COVID-19 disease. Through so-called drug repurposing, the conversion of existing active ingredients with a known safety profile or drugs already approved for other indications, Fraunhofer scientists want to quickly identify new active ingredients against COVID-19 and develop therapies. The DRECOR project builds on this drug repurposing approach and pursues three main objectives: First, suitable drug molecules that act in the respiratory tract and lungs are to be found and formulated for systemic or inhalative administration. In addition, a prototype of a smart medical device for inhaled drug delivery will be built, which can be used in clinical studies. In addition, complex in vitro models and test systems are to be established, which can also be used in other projects for other indication areas. In the longer term, the project partners want to establish a multidisciplinary network and provide suitable procedures for the formulation and administration of drugs in order to be better prepared for future pandemics. Seven Fraunhofer Institutes are cooperating in the DRECOR project, coordinated by Fraunhofer IME.

  • Fraunhofer Institute for Applied Polymer Research (IAP)
  • Fraunhofer Institute for Biomedical Engineering (IBMT)
  • Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB)
  • Fraunhofer Institute for Molecular Biology and Applied Ecology (IME)
  • Fraunhofer Institute for Silicate Research (ISC)
  • Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM)
  • Fraunhofer Institute for Cell Therapy and Immunology (IZI)
  • Fraunhofer Project Center for Drug Discovery and Delivery at Hebrew University of Jerusalem (Israel)

more information: Website of the ITEM

BEAT-COVID: With novel therapies against the pandemic

The current SARS coronavirus 2 pandemic with all its implications for society - both in health and economic terms - shows how urgent it is to develop new therapies to treat COVID-19. At the same time, it highlights the need to be well prepared for any new viral infections that arise in the future. In order to counter this pandemic and to be prepared for new pandemic pathogens that will emerge in the future, Fraunhofer researchers in the BEAT-COVID project are developing independent, novel therapeutic strategies and are also building platform technologies that will enable them to develop new drugs against future, as yet unknown pathogens in a very targeted and rapid manner. Five Fraunhofer Institutes and cooperating universities, coordinated by the Fraunhofer ITEM, are jointly pursuing three objectives with their expertise in preclinical and clinical drug development: to prevent the virus from entering the cell, to directly combat the virus and finally to regulate the excessive immune reaction triggered by the virus.

Contact:   Prof. Dr. Jens Hohlfeld

Partners:

  • Fraunhofer Institute for Applied Polymer Research (IAP)
  • Fraunhofer Institute for Silicate Research (ISC)
  • Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM)
  • Fraunhofer Institute for Cell Therapy and Immunology (IZI)
  • Fraunhofer Institute for Reliability and Microintegration (IZM)

more information: Website of the ITEM [1; 2]

RENACO: Pancreas medication Nafamostat against COVID-19

In view of the pandemic spread of SARS-CoV-2 and the associated increase in the number of deaths worldwide, effective drugs and vaccines are urgently needed. To accelerate this process, drugs already approved for the treatment of other diseases are being tested for their potential efficacy against the novel coronavirus. Scientists of the German Primate Center (DPZ) - Leibniz Institute for Primate Research in Göttingen and the Fraunhofer Institute for Toxicology and Experimental Medicine ITEM in Hannover are now receiving 1.6 million euros from the German Federal Ministry of Education and Research (BMBF) for a joint project to study the efficacy of nafamostat.

Contact:   Prof. Dr. Armin Braun

Partners:

  • German Primate Center Göttingen (DPZ)
  • Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM)

Funding: 1.600.000 € from the Federal Ministry of Education and Research (BMBF)

more information: Website of the ITEM

Preparation of SARS-CoV-2 neutralizing monoclonal antibodies from blood samples of reconvalescent COVID-19 patients

The project aims to isolate monoclonal antibodies from B-memory cells of patients that have recovered from COVID-19 to use them in therapy. These antibodies will be tested for their ability to bind and neutralize the new coronavirus and promising candidates will be transferred to clinical tests as soon as possible. This goal will probably be reached sooner using antibodies from B-cells than antibodies from synthetic libraries because the natural antibodies from the human body are less likely to show unexpected cross reactions in patients.

Contact:   Prof. Dr. Ulrich Kalinke

Partners:

  • Helmholtz Center for Infection Research (HZI)
  • Hannover Medical School (MHH)
  • Memo Therapeutics AG
  • TWINCORE – Centre for Experimental and Clinical Infection Research

Funding: 177.000 € from the Lower Saxony Ministry of Science and Culture

More information: Website of Memo Therapeutics AG

Assessment and development of an inhalable inhibitor of the new coronavirus

Using highly intensive X-ray light from the synchrotron source BESSY II at the HZB, scientists were able to identify the three-dimensional architecture of the main protease of SARS-CoV-2. This enzyme is involved in the proliferation of the virus. With the aid of the crystal structure, a formerly developed lead compound could be optimized into a potent inhibitor at the University of Lübeck. Large amounts of the inhibitor were tested in healthy mice at the HZI and it was shown to not be toxic. The compound is most effective if it is applied under the skin or inhaled. In further experiments, the compounds will be optimized using medicinal chemistry and their pharmacokinetic properties will be characterized.

Original publication: Linlin Zhang et al., Crystal structure of CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors, Science 2020

Contact:   Prof. Dr. Mark Brönstrup

Partners:

  • Helmholtz Center for Materials and Energy (HZB)
  • Helmholtz Center for Infection Research (HZI)
  • University of Lübeck

Funding: 120.000 € from the European Union (EU) and 24.904 € from the German Centre for Infection Research (DZIF)

More information: Website of the HZI

Quantifying the anti-SARS-CoV-2 activity of antibodies and antiviral substances

The aim of the research efforts is the development of an in vitro neutralization test for SARS-CoV-2 using clinical isolates. In the next step, a more sensitive high-throughput neutralization test for SARS-CoV-2 will be established that is based on GFP-expressing viruses as well as real-time tracking and quantification of viral fluorescence output. Additionally, the team will develop new technologies for the manufacturing of recombinant viruses, which will carry for example phosphorescence reporter genes. Furthermore, the research group collaborates with the industry partner YUMAB on neutralizing antibodies against SARS-CoV-2.

Contact:   Prof. Dr. Dr. Luka Cicin-Sain

Partners:

  • Helmholtz Center for Infection Research (HZI)
  • Technical University of Braunschweig
  • YUMAB GmbH

Funding: 217.000 € from the Lower Saxony Ministry of Science and Culture

More information: Website of the HZI

SCORE: Swift COronavirus therapeutics REsponse

The HZI is involved in the EU project SCORE (Swift COronavirus therapeutics REsponse). SCORE will develop antiviral medication that can be used as short-term and medium-term treatment for patients and can contain the spread of SARS-CoV-2.

Contact:   Dr. Katharina Rox

Partners:

  • Academisch Ziekenhuis Leiden (Netherlands)
  • Aix-Marseille Université (France)
  • Eidgenössisches Department des Innern (Switzerland)
  • Helmholtz Center for Infection Research (HZI, Germany)
  • Janssen Pharmaceutica NV (Belgium)
  • Katholieke Universiteit Leuven (Belgium)
  • Universität Bern (Switzerland)
  • University of Lübeck (Germany)
  • Universiteit Utrecht (Netherlands)

Funding: 2.576.062 € from the European Union (EU)

More information: Website of the HZI and the EU

Development of neutralizing antibodies against SARS-CoV-2

People that have successfully recovered from a SARS-CoV-2 infection have different protecting antibodies in their blood. Some of these compounds are especially effective. The aims of the team of RESIST spokesperson Professor Schulz and the MHH Professors Blasczyk and Haverich are to discover highly potent antibodies, to produce them in the lab using genetic engineering and to apply them as protection against infection and as therapy for the infected.


“We are looking for antibodies that prevent the virus from binding to the cells – that act neutralizing – and that, if necessary, detect emerging variants”, says Professor Dr. Thomas Schulz, head of the MHH institute of virology and RESIST spokesperson. These broad-spectrum neutralizing antibodies are already successfully applied against HIV to suppress the proliferation of the HI-virus in the human body. First, the team detects highly potent antibodies in blood samples of convalesced patients. “We especially need samples from people, who have produced large amounts of protecting antibodies after recovering from a COVID-19 infection. This applies to about 10 to 15 percent of infected patients”, says Professor Schulz.

Contact:   Prof. Dr. Thomas Schulz

Partners:

  • Hannover Medical School (MHH)
  • University of Veterinary Medicine Hannover Foundation (TiHo)
  • University of Lübeck

Funding: 1.245.000 € from the Lower Saxony Ministry of Science and Culture 

More information: Website of RESIST

MANCO: Monoclonal Antibodies against 2019-New COronavirus

Researchers from TiHo are involved in the big EU collaboration project „MANCO: Monoclonal Antibodies against 2019-New COronavirus“ to analyze monoclonal antibodies. The antibodies are acting against a glycoprotein, which is located on the viral envelope. The glycoprotein is responsible for binding the host cell membrane, fusing it to the viral membrane and enabling the delivery of viral DNA into the host cell. The monoclonal antibodies are a promising approach to prevent the interaction prophylactically and therapeutically.

Contact:   Prof. Dr. Ab Osterhaus

Partners:

  • Consejo Superior de Investigaciones Científicas (Spain)
  • CR2O BV (Netherlands)
  • Erasmus Universitair Medisch Centrum Rotterdam (Netherlands)
  • Finovatis (France)
  • Harbour Antibodies BV (Netherlands)
  • International Alliance for Biological Standardization (France)
  • University of Veterinary Medicine Hannover (TiHo, Germany)
  • Universiteit Utrecht (Netherlands)

Funding: 3.034.581 € from the European Union (EU)

More information: Website of the EU

The EU consortium ATAC

Scientists from the department of biotechnology of the Technical University of Braunschweig are a part of a research project that aims to develop new antibody therapies for the treatment of severe coronavirus infections. The international project has participants in Sweden, Belgium, Italy and Switzerland and is part of the international research network ATAC (Antibody Therapy Against Coronavirus) that aspires to develop antibody-based therapies against the COVID-19-causing virus SARS-CoV-2.

Contact:   Prof. Dr. Michael Hust

Partners:

  • Fondazione IRCCS Policlinico San Matteo (Italy)
  • Fondazione per l'istituto di Ricerca in Biomedicina (Switzerland)
  • Joint Research Centre of the European Commision (Belgium)
  • Karolinska Institutet (Sweden)
  • Technical University of Braunschweig (Germany)

Funding: 2.995.040 € from the European Union (EU)

More information: Website of the EU and the ATAC consortium

CORAT: CORona Antibody Team

The CORAT consortium recently accomplished the creation of protective, completely natural, human antibodies that defend 100% of cells from SARS-CoV-2 infection, which was verified by the Helmholtz Center for Infection Research. CORAT is a consortium of academic and industrial partners with the common goal to develop a passive immunotherapy against COVID-19 that uses completely human monoclonal antibodies to inhibit SARS-CoV-2 infection.

Based on the research results of the consortium, the biotechnology company YUMAB, a spin-off of the Technical University of Braunschweig, founded CORAT Therapeutics GmbH, which is now bundling the development work in order to develop an antibody drug against COVID-19 as quickly as possible. The state of Lower Saxony, together with the investment company NBank Capital and a group of investors from Braunschweig, are participating in the newly founded biotech start-up.
 

  • Bayer AG
  • CORAT Therapeutics GmbH
  • Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM)
  • Helmholtz Center for Infection Research (HZI)
  • Hannover Medical School (MHH)
  • Technical University of Braunschweig
  • Tübingen University Hospital
  • YUMAB GmbH

Funding: Lower Saxony Ministry of Economics, Labour, Transport and Digitalisation, Lower Saxony Ministry of Science and Culture & NBank Capital Beteiligungsgesellschaft mbH

More information: Websites of CORAT and CORAT Therapeutics GmbH

Immunovid‐19: Preventing SARS-CoV-2 from entering the cells

There are several different therapeutic approaches against SARS-CoV-2. One is to prevent the virus from entering the host cell. This is the development topic that the Fraunhofer ITEM and the Helmholtz-Zentrum Dresden-Rossendorf are addressing as partners in the Immunovid-19 project. Together, they aim to develop a therapeutic approach to prevent the coronavirus SARS-CoV-2 from entering the cells by means of a fusion protein with the soluble domain of the ACE2 protein. A recombinant CHO production cell line is currently being developed to produce the fusion protein.

Contact:   Dr. Corinna Lüer

Partners:

  • Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM)
  • Helmholtz-Zentrum Dresden-Rossendorf

More information: Website of the ITEM

Safe-Anticorona: Investigating pharmacokinetics and safety of monoclonal antibodies against SARS-CoV-2 in models

Monoclonal antibodies, which were obtained from the immunoplasm of convalesced COVID-19 patients and are able to inactivate the virus (neutralizing antibodies), are considered to be promising drugs. Scientists at the Fraunhofer ITEM intend to use a special lung model to investigate the safety and pharmacokinetics (describes the totality of all processes to which a drug is subject in the body: the uptake, distribution in the body, biochemical conversion and degradation and excretion of a drug) of a monoclonal antibody. The model they use is the isolated perfused rat lung (IPL). This ex vivo organ model is used to investigate the safety, bioavailability and kinetics of intravenously administered antibodies. In addition, the researchers will investigate whether an intravenously administered antibody reaches the target site of SARS-CoV-2 infection, i.e. the lung, or whether inhalation administration is more promising.

Contact:   Dr. Christina Hesse

Partners:

  • Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM)

more information: Website of the ITEM

iCAIR uses synergies for the development of new drugs against SARS-CoV-2

Researchers of the international consortium iCAIR® are working on the development of new anti-infectives for the treatment or prevention of clinically significant infectious diseases of the respiratory tract caused by bacteria, viruses and fungi - they have now started a project to develop drugs against the coronavirus SARS-CoV-2.

Contact:   Prof. Dr. Armin Braun

Partners:

  • Fraunhofer Institute for Molecular Biology and Applied Ecology (IME)
  • Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM)
  • Griffith University (Australia)
  • Helmholtz Centre for Infection Research (HZI)
  • Hannover Medical School (MHH)
  • TWINCORE - Centre for Experimental and Clinical Infection Research

more information: Website of  iCAIR [1, 2] and interview with project leaders

Specifically cleaving peptidases

Peptidases such as cathepsin and TMPRSS activate the "spike" protein for the passage of CoV into the lung cell. Inhibitors for these peptidases such as camostat are potential therapeutics. The Institute is working on such specifically cleaving peptidases. Separation techniques as well as FRET assays and partial sequencing methods (nLC-QTOF-MS/MS) are established. Thus, medically oriented research groups at the MHH can be methodically supported, as is already practiced with the Borlak group. (Part of the project SalModuPep: Salty taste enhancing peptides from enzymatically produced protein hydrolysates)

Contact:   Prof. Dr. Dr. Ralf Günter Berger

Partners:

  • Gottfried Wilhelm Leibniz University Hannover (LUH)
  • Hannover Medical School (MHH)

Funding: 217.121 € from the Federal Ministry of Food and Agriculture

Investigation of Silvestrol as a plant-based compound with antiviral activity against the coronavirus 2019-nCoV

Silvestrol is a natural substance from Asian mahogany plants. It has virus-inhibiting properties against the hepatitis E virus and, as recently discovered, also against the coronavirus 2019-nCoV. It is difficult to produce chemically and must therefore be extracted from the natural source in the Indonesian jungle. Silvestrol inhibits an endogenous enzyme of the host on which the coronaviruses depend in order to produce their own proteins. Because of this inhibiting effect of Silvestrol, the virus is eventually unable to reproduce. 
Silvestrol is therefore a unique starting point for the development of a drug against the coronavirus. This therapeutic approach is an alternative to the possibility of developing an antiviral vaccine. A medicinal-chemical research programme on Silvestrol involves the synthesis of a so-called library of Silvestrol derivatives and aims to improve antiviral properties with reduced side effects. (Part of the project SILVIR: Development of the natural compound silvestrol as antiviral drug candidate for hepatitis E virus and emerging RNA viruses)

Contact:   Prof. Dr. Andreas Kirschning

Partners:

  • Friedrich-Loeffler-Institut Federal Research Institute for Animal Health
  • Gottfried Wilhelm Leibniz University Hannover (LUH)
  • Ruhr University Bochum (RUB)

Funding: 1.104.115 € from the Federal Ministry of Education and Research (BMBF)

more information: Website of the BMBF and the RUB

Itaconic acid and other Nrf2 inducers as treatment for COVID-19 (COVID Protect)

More information will follow.

Contact:   PD Dr. Frank Pessler

Partners:

  • Helmholtz Center for Infection Research (HZI)
  • Hannover Medical School (MHH)
  • TWINCORE – Centre for Experimental and Clinical Infection Research

Funding: 152.423 € from the Federal Ministry of Education and Research (BMBF)

Peptide microarray-based discovery of epitopes with SARS-CoV-2 neutralizing activity from human sera

More information will follow.

  • Helmholtz Center for Infection Research (HZI)