Eight COVID-19 projects led from Gothenburg with support from SciLifeLab

Just after the start of the pandemic, SciLifeLab, together with the Knut and Alice Wallenberg Foundation (KAW), launched a national challenge for researchers to create a comprehensive research program in nine fields to fight the disease. The call totaled SEK 50 million. Of the 282 submitted proposals, 67 have been funded, of which eight projects will be conducted by researchers at the University of Gothenburg and Sahlgrenska University Hospital.

Antiviral effect

Kristina Nyström, Associate Professor and virologist at Microbiology, has been awarded SEK 300,000 for the project already underway to test drug libraries for antiviral effects against SARS-CoV-2 in cell cultures. After some intense efforts at Microbiology, the lab is now in operation.

“So far, we have tested the ability of antibodies to neutralize virus infections. We now have virus cultures with different varieties of the virus where we have begun testing different antiviral drugs,” says Kristina Nyström.

Slow down or block the virus

The project is lead by Göran Karlsson, professor and the director of the Swedish NMR Centre at the Faculty of Science, and it is being conducted in collaboration with several researchers both in Gothenburg and in Umeå. The project has received nearly SEK 500,000 from the call for proposals. By using advanced NMR methods, they will try to find drugs or fragments that can be developed into drugs, which block two central functions in the SARS-CoV-2 virus. The goal is to block the enzymes that cut up the polyproteins into functioning units, and the spike protein’s ability to bind to receptors.

“We will produce these proteins and then screen nearly all existing drugs, where we then test the most promising candidates in cell cultures to see how they effect the virus,” says Göran Karlsson. “We are trying to knock out functions that the virus needs to enter cells and multiply. Ideally, we will find a molecule that slows it or blocks it from developing. This could become a drug used to treat COVID-19.”

Identify who risks serious illness

Lars-Magnus Andersson, Associate Professor and senior physician within infection, is leading another project, which includes Ola Hammarsten, Magnus Gisslén, Ali Harandi and others. The project has received SEK 1.3 million to try to identify markers for serious illness with COVID-19 using transcription analysis of microRNA and a technique called Proximity Extension Assay (PEA).

“We hope to contribute to the early identification of patients with risk for serious illness and in this way improve planning and treatment of the patient. Hopefully, the project will also allow doctors to determine which patients have the greatest benefit of treatments like antiviral drugs,” says Lars-Magnus Andersson.

Part of the project will also focus on the impact COVID-19 infections have on the heart.

Long-term immunity

Davide Angeletti, Mats Bemark and Anna Lundgren are together leading a collaborative project that has been awarded SEK 1.5 million, where many other researchers at GU are also participating.

“We have put together a really good team of researchers, whose different expertise will allow us to study how immunity with COVID-19 is developed and maintained based on many different aspects,” says Davide Angeletti.

Blood samples from patients admitted to the hospital for COVID-19 show a large increase in B cells that produce antibodies, and the project will study what type of antibodies are produced, which of these are specific for the SARS-CoV-2 virus and where in the body the B cells are targeted.

Since this is a lung infection, it is very important to understand whether these cells, which are called plasma blasters, migrate from blood to lungs and also to understand the specificity and function of the antibodies that are produced by these cells.

“Thanks to our partner Magnus Gisslén, we will gain access to blood samples from COVID-19 patients throughout their hospitalizations and have the opportunity to then follow up some of these patients several months after they have been released from the hospital,” explains Davide Angeletti.

The project also has the goal of understanding whether the patients develop immunity specifically for SARS-CoV-2 and whether this is maintained in the long-term and can contribute to protection from reinfection.

“Immunological memory normally isn’t very long for other coronaviruses, and we are in a hurry to find out whether this is also the case for SARS-CoV-2, since it has consequences for the ability to develop vaccines and inform general policy.”

The surface protein of the virus

Fredrik Sterky, Gunnar C Hansson and Ka-Wei Tang are co-applicants in a project that received SEK 400,000, where the core facility Mammalian Protein Expression (MPE) also plays an important role.

“We will make variants of the virus's surface protein and express it in cell lines that can recreate its extensive glycosylation. We should be able to use the protein to set up clinical antibody tests, but it will also be distributed to other researchers who want to study it,” says Fredrik Sterky, who is affiliated with the Wallenberg Center for Molecular and Translational Medicine (WCMTM), where he usually focuses on brain synapses.

“This is an entirely new way of working! I am not a virologist but try to contribute to the bigger picture with the parts that are our expertise. At the same time, I try to maintain my regular research, which is a challenge in itself under current conditions.”

Building biobanks

Two funded projects deal with biobanking. Professor Magnus Gisslén has received SEK 1.7 million to build a biobank that will include samples of plasma and serum from patients with different degrees of severity with COVID-19. Different projects to study immunology, immunity, virology and impact on the brain and heart have begun. The biobank will also be a resource for studies outside of Sahlgrenska University Hospital.

Åsa Torinsson Naluai is leading another biobank project studying immunity against COVID-19. The project has received nearly SEK 1 million and is a collaboration between Biobank Core Facility and Biobank West. The project hopes to contribute with more knowledge on the biological mechanisms that result in certain individuals being more severely effected by a virus while others have no symptoms.

“For many years we have tried to understand common public health ailments like diabetes, but we haven’t gotten very far. If we understand more about this virus, maybe it can also lead to explanations that we haven’t been able to reach before and help us develop good data for new interpretations of other diseases,” says Åsa Torinsson Naluai.

The project will study antibodies in the blood and virus in the saliva, throats and noses of patients who have come to Sahlgrenska University Hospital to give samples. Analysis of the first samples will begin at the latest in August 2020.

“We will be able to create a unique patient cohort of asymptomatic, mild and severe cases of SARS-CoV-2-infected individuals. Based on this, we can then identify genetic variations in connection with severe cases of SARS-CoV-2 infection.”

Projects led by researchers in Gothenburg funded by the call

Biobanks for Covid-19 research

• Building Capacity – the Sahlgrenska Covid-19 Biobank, Magnus Gisslen, University of Gothenburg
• Assessment of SARS-CoV-2 specific antibodies in adults, and building a repository of samples from seroconverted asymptomatic adults, Åsa Torinsson Naluai, University of Gothenburg

High-throughput and high-contenct serology

• Optimized expression of the SARS-Cov-2 Spike protein in mammalian cells for serology testing and functional studies, Fredrik Sterky, University of Gothenburg
• Rapid development of novel antibody assays diagnosing Covid-19, Jan-Åke Liljeqvist, University of Gothenburg

Biomarkers and systems immunology

• Prediction of severe disease in Covid-19, Lars-Magnus Andersson, University of Gothenburg
• Dynamics and longevity of the specific adaptive immune response in COVID-19 patients, Davide Angeletti, University of Gothenburg

Drug discovery and repurposing of drugs

• FragCor, Göran Karlsson, University of Gothenburg
• Rapid testing for treatment of Covid-19, Kristina Nyström, Sahlgrenska University Hospital
  
  Text: Elin Lindström and Charbel Sader
  Photo: Johan Wingborg