Intensive research on SARS-CoV-2

Since the beginning of 2020, the novel coronavirus SARS-CoV-2 has continued to spread around the world. New infections and deaths are on the rise globally and humanity is facing what is probably the worst economic crisis since 1970.

In this situation, Würzburg can make an important contribution to solving the problem: Already in January, research teams of Professor Jörg Vogel, an RNA expert and infection biologist, started tackling the novel coronavirus whose genome consists entirely of RNA.

Jörg Vogel is the Director of the Institute for Molecular Infection Biology (IMIB) at the University of Würzburg and of the Helmholtz Institute for RNA-based Infection Research (HIRI) in Würzburg, a branch of the Helmholtz Centre for Infection Research (HZI) in Braunschweig. Vogel and his team are focusing on two major fields of research since neither a vaccine nor approved drugs to combat the new virus are currently available.

Searching for drugs to treat SARS-CoV-2

For one thing, the Würzburg research groups want to understand the virus at the molecular level in order to identify new drug targets. The team of Dr. Emmanuel Saliba, for example, concentrates on single-cell RNA sequencing to gain insights into the host's defence responses to infections and to study the impact of these responses on the disease course.

SARS-CoV-2 first attacks cells of the upper respiratory tract. Therefore, it is crucial to understand how the virus gains entry into the host cell and subsequently "hijacks" it. Saliba uses an RNA sequencing technology recently developed in Würzburg to visualise the course of the infection of individual cells over time. This enables him to identify critical moments after the virus has entered the cell. Moreover, the technique is used to discover regulatory networks and pinpoint additional targets for new drugs.

Neva Caliskan, an assistant professor conducting research at the HIRI, is working to identify and characterise so-called recoding mechanisms in RNA viruses and their regulatory properties in infections.

A messenger RNA usually contains the blueprint for a protein. But some viruses, including coronaviruses, have found ways to boost their limited genomic storage capacity, often using a single messenger RNA to produce multiple proteins. This mechanism is essential for the virus because without it no new viruses can be produced in the host cell. Once researchers have gained a better understanding of how SARS-CoV-2 makes proteins, they could develop new drugs to treat the virus on this basis.

Two research groups led by assistant professor Redmond Smyth and Dr. Mathias Munschauer, two early career researchers at the Helmholtz Institute, want to find out which factors lead to viral replication.

Taking a holistic approach, they identify the interaction partners of the viral RNA on the host side. By doing so, they are able to determine which host factors are essential for the replication of the virus. At the same time, this allows identifying potential target molecules for new antiviral treatments.

RNA-based vaccines

RNA-based vaccines are a focal area of interest. By introducing weakened virus or viral fragments, which are both external antigens, conventional vaccines teach the human immune system how to deal with an infection. RNA vaccines in contrast deliver the viral blueprint so that the organism can produce the matching antigens itself and use them to train the immune system.

It is easy to modify the RNA sequence in the laboratory and thus the blueprint of the virus, facilitating the production of different vaccines in a short time. "Such a platform technology is highly valuable in the event that the virus mutates," says Professor Vogel.

What is more, large amounts of RNA vaccines can be produced relatively quickly and at low cost. They do not have to be cooled, they are stable and hence easy to transport.

The Würzburg teams are experts in RNA-based infection research. They will use their expertise to further accelerate the development of a vaccine. In a first step, suitable target structures of the virus will be identified by means of high-throughput sequencing methods. These structures will then be used to derive custom-fit RNA sequences for vaccines that can be developed in a preclinical phase.

Cooperation is key

By pooling the Würzburg expertise, Jörg Vogel hopes to beat the virus more quickly: "Scientific cooperation at a local, national and international level is key. We in Würzburg and our colleagues around the globe are studying the virus with all techniques currently available to understand it at the molecular level, hoping that this will lead to the development of vaccines and effective drugs as quickly as possible."