Annika Kratzel - SARS-CoV-2

Key factors of the SARS-CoV-2 infection may serve as points of attack for medicaments

You wrote your doctoral thesis during the coronavirus pandemic: What was the context and which objective did you have?

Generally, when a new, previously unknown virus appears, no medicaments or vaccinations usually exist to combat it. This was also the case at the beginning of the SARS-CoV-2 pandemic. There are several possibilities to develop medicaments against viruses. On the one hand, there are medicaments that act directly against the virus. In this case a virus may “escape” from the medicament by forming new variants. In contrast, medicaments that block the viruses’ critical mechanisms in the human cells, may prevent or inhibit an infection. One objective of my PhD project was to gain a better understanding of SARS-CoV-2 infections in cells in order to identify mechanisms that could serve as points of attack for medicaments.

Can you explain how the coronavirus infects a host cell?

Human cells comprise about 20 000 factors that each have a particular task to ensure that the cells function well. For a successful infection the SARS-CoV-2 “steals” the task of some of these factors.

The most important steps of a SARS-CoV-2 infection are, chronologically:

1. Virus entry into the cells.

2. Release of the virus’ genetic information into the cells.

3. Replication of the virus’ genetic information.

4. Packaging the virus’ genetic information into new viruses.

5. Exit of the virus from the cells.

The challenge for me was to identify which of these 20 000 factors have a “key function” for the SARS-CoV-2 infection. By applying a specific method my colleagues from the Volker Thiel group and I identified 3 important factors that are suitable as targets for medicaments to prevent SARS-CoV-2 infections.

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How exactly did you proceed so as to analyse which of the 20 000 factors play an important role for a SARS-CoV-2 infection?

We used a “gene shear technique” (CRISPR) to discover factors in a cell which are indispensable for a SARS-CoV-2 infection. With the “gene shear technique” we made a single “cut out” from each of the 20 000 factors and thereby detected 3 factors without which the SARS-CoV-2 cannot replicate in the cells. A difficulty here was to find a balance between eliminating the virus and simultaneously preserving the cells, such that they could still function well in spite of the loss of the factors.

Were you able to successfully identify these factors?

The gene shear technique enabled us to identify 3 factors “TMEM41B, FKBP8 and MINAR 1“ as important cellular factors for a SARS-CoV-2infection. These Erkenntnisse led to a better understanding of SARS-CoV-2 in the cell.

What impact do your results have for the combat against coronavirus in the future?

This work is a good example of how fundamental research and its application to medicine can overlap. On the one hand we have found that “TMEM41B, FKBP8 and MINAR1” factors are important for a SARS-CoV-2 infection and thus deepened our understanding of the virus. On the other hand we have discovered points of attack for possible COVID-19 medicaments.

What did you particularly like in your PhD work?

I was thrilled that our work had the potential to make a positive contribution against the pandemic. It was particularly exciting to study the course of the pandemic in the laboratory in more or less real time. I not only realised how long the path is from the results of fundamental research to the production of medicaments or vaccines but also the importance of precision and efficiency to our work.

How was your time at the IVI? What did you like in particular?

Best of all I liked the collaboration with many great colleagues and the extent to which I could learn from them. I made many friends during my time at the IVI. The work was fun every day.

What are you going to do now?

After my PhD I would like to stay in research. As I really enjoyed my time at the IVI and I still have a lot to learn, my preference is to remain here. My principal focus will then be on other coronaviruses and techniques. We want to visualise and track the genome of coronaviruses under a microscope during a replication cycle in the cell. I am looking forward to my new project.

Last modification 08.02.2023