Many different research projects on SARS-CoV-2 are carried out in the Cluster of Excellence RESIST – always with the aim of protecting and treating people in the best possible way. Professor Schulz gives an overview of the work:

Professor Schulz, what are RESIST scientists researching with regard to SARS-CoV-2?

The aim of RESIST is to improve our understanding of the molecular basis of an increased susceptibility to infectious disease together with the causative bacterial or viral pathogens. These new insights will in the long term lead to new approaches to diagnosis and therapy. When RESIST started at the beginning of 2019, the new coronavirus SARS-CoV-2, had not yet appeared on the scene and we did initially not have any plans to work on the new disease, CoVID. However, CoVID appears to predominantly affect individuals with particular risk factors, some of which are known, such as obesity, diabetes, hypertension, etc. but others are not. CoVID therefore falls squarely into the RESIST remit and we have therefore begun to harness the expertise and strengths of RESIST scientists towards working on CoVID and SARS-CoV-2. We are working on several topics in parallel, as explained below. These new projects have recently been awarded additional substantial funding from the Lower Saxony Ministry of Science and Culture, for which we are very grateful, as it allows us to kick-start a substantial research programme on this new disease.

We are looking for protective antibodies and vaccines.
We want to develop antibodies that prevent the virus from binding to the human cell and can therefore block the infection with SARS-CoV-2. Such antibodies are referred to as ‘neutralizing antibodies’. We are looking for antibodies that can neutralize the virus at very low concentrations and can do so for possibly emerging virus variants. Such broadly neutralizing antibodies are already being successfully used in HIV-infected patients, for example, to suppress HIV replication.
We are searching for these particularly good antibodies in the blood of patients who have already survived the CoVID disease. We will then produce these antibodies with recombinant gene technology in the laboratory. In this way we hope to produce them in large quantities and to eventually use them to treat severe infections. Such a therapeutic agent could be available next year at the earliest.
For this work, we are using the expertise of RESIST researcher Professor Dr. Thomas Krey from the University of Lübeck. He has a lot of experience in the field of elucidating structures of viral and cellular proteins that play key roles in infection processes. Professor Dr. Rainer Blasczyk, head of the Insitute of Transfusion Medicine, and Professor Dr. Axel Haverich, Head of the Department of Cardiothoracic and Vascular Surgery, lead the recruitment of convalescent patients for this study.

In parallel, we are conducting a preclinical trial on a potential coronavirus vaccine: Professor Dr. Reinhold Förster, head of the MHH Institute of Immunology, is testing a new vaccine candidate in a mouse experiment which explores a particular form of application for this vaccine candidate.

We are looking for substances that inhibit the replication of viruses
We are pursuing two strategies to achieve this:
Led by our RESIST colleague Professor Pietschmann from the Twincore Institute, we are screening around 13,000 substances, which have either already been licensed for therapeutic use against other diseases, or for which there is already initial clinical experience – for example, substances that have already undergone safety testing in healthy volunteers. We are investigating whether they are effective against the replication of SARS-CoV-2 and if it might be possible to develop them into new drugs. Depending on how much clinical experience is already available for any compound that will be identified in this manner, making them available for clinical use could take between one and several years’ time.
In the other strategy, we want to find completely new targets for inhibitors and are asking ourselves which substances could inhibit all seven known coronaviruses – and thus perhaps also the next coronavirus to hit mankind. To do this, we are screening up 100,000 substances. We hope that, on the basis of these results, it may be possible to develop a drug with broad activity against coronaviruses. However, this will take five to ten years. Professor Dr. Thomas Pietschmann from TWINCORE – Centre for Infection Research and I are working on this together with other colleagues from the Helmholtz Center for Infection Research (HZI).

We are investigating how the immune system reacts to the virus.
RESIST scientists are also investigating how the innate and acquired immune systems react to SARS-CoV-2. For example, how do T cells recognise this virus? Professor Dr. Markus Cornberg, MHH Clinic for Gastroenterology, Hepatology and Endocrinology, Professor Britta Eiz-Vesper, Institute of Transfusion Medicine, and Professor Dr. Immo Prinz, MHH Institute of Immunology, and other colleagues are investigating these questions. The aim is to perhaps harness the power of antiviral T cells to treat COVID.

Are there genetic reasons for an increased severity of COVID and a higher susceptibility to SARS-CoV-2?
In RESIST we had already initiated a cohort of senior individuals to investigate in which way the immune system ages and why this leads to an increased susceptibility to infectious disease. COVID is particularly severe in people older than 70 years and therefore represents a problem at the core of the RESIST research programme. We will therefore study the immune responses, and the genetic background, of COVID patients and compare our findings to those obtained in our cohort of healthy elderly citizens. In this manner, we want to find out why some people become seriously ill although they have no previous illnesses. These results should also provide us with approaches for new therapies.

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