Illuminate How the Virus Replicates in the Body
A team around Christian Eggeling and Pablo Carravilla aims to visualize how the coronavirus enters the cell and identify its points of attack
Sars-CoV-2 belongs to the coronavirus family. They are so named because their many spikes resemble a crown. With these spikes, the so-called spike proteins, the virus docks onto the human cell and hijacks it. In this way, the virus introduces its operating program into the cell, thereby causing it to produce new viruses. The pathogen uses its host to replicate.
Christian Eggeling and Pablo Carravilla want to find out how to block this process. „To do this, we are investigating how viruses enter cells, in particular, which processes take place at the cell membrane, the gateway to the cell,“ explains Christian Eggeling, who heads the „Biophysical Imaging“ research department at Leibniz IPHT. To study the molecular structure and dynamics of the virus, the researchers use super-resolution fluorescence STED microscopy; this bypasses the resolution limit of optical microscopy and makes it possible to visualize dynamic processes in the tiny viruses in detail.
Block the passage of the virus
Using super-resolution imaging, Eggeling and Carravilla have already studied how HI viruses, causing the AIDS disease, spread between living T helper cells and observed how the virus reacts to neutralizing antibodies. „In the process, we have identified potential points of attack where antiviral drugs can be targeted,“ reports Christian Eggeling: distinct characteristics of the cell and virus membrane to deteriorate viral docking to the cells, as well as the gateway through which the HI virus – after it has replicated inside it – exits the cell again to infect other cells.
To figure out how SARS-CoV-2 enters human cells, the researchers make so-called pseudoviruses – a trick they also use in their study of the AIDS pathogen. „They have a surface like the real virus and the same ability to penetrate cells, but they are not capable of reproducing and are therefore not pathogenic,“ explains Pablo Carravilla. This means that experiments can also be carried out in laboratories with low-security levels.
The virus-like particles consist of a core with lentiviral genes – the HI virus also belongs to the lentivirus genus – and an envelope with the surface proteins of SARS-CoV-2. The researchers also incorporate a fluorescent protein that makes the virus-like particles visible under the microscope. The research team has also made these pseudoviruses available to other scientists for their own measurements.
In order to observe the processes in which pathogens such as viruses, bacteria, or fungi infect whole organisms and not only in individual cells, but also to find out how this infection occurs in a more natural environment of cell layers, the IPHT researchers, as well as many other research teams throughout Jena, are collaborating with Alexander Mosig and his research group at the University Hospital. Mosig and his team are developing biochips that replicate complex organ functions in order to use these chips to study specific aspects of these organ functions under laboratory conditions. „For many pathogens such as SARS-CoV-2 but also other viruses such as the influenza virus, the trigger of the annual flu, these would be lung chip models – a lung on a chip,“ says Christian Eggeling. The researchers are currently laying the groundwork for this, for example by optimizing the advanced imaging within the chips.
Together with researchers from Jena University Hospital led by Ralf Mrowka, from Ilmenau Technical University and Jürgen Popp’s „Spectroscopy / Imaging“ research department at Leibniz IPHT, Eggeling’s team is also developing an optical-photonic detection method to quickly and efficiently diagnose and quantify SARS-CoV-2 from patient samples. Funded by the Free State of Thuringia, the „SARS-rapid“ research group at the Thuringia Innovation Center for Medical Technology Solutions (ThIMEDOP) is investigating how the novel coronavirus interacts with the host cell. Hereby, also the pseudoviruses are further optimized.
By drug cab to the site of inflammation
A novel method for treating infections and inflammatory reactions directly at the site of inflammation with the help of tailored nanoparticles is being developed by an interdisciplinary research team from chemistry, biochemistry, physics, materials science, medicine, and pharmacy at the Polytarget Collaborative Research Center at the University of Jena, in which Leibniz IPHT is also involved with several research departments.
Together with chemist and SFB spokesman Ulrich Schubert and intensive care physician Michael Bauer, Christian Eggeling and his team are investigating carriers for antiviral substances using Sars-CoV-2 as an example. „The basis are virus-like, polymeric nanoparticles. These are supposed to protect the substances and guide them to the right tissue cells,“ says Christian Eggeling. The nanoparticle treatment can be thought of as a cab with GPS, explains Michael Bauer, director of the Department of Anesthesiology and Intensive Care Medicine at the University Hospital and deputy spokesman for the Collaborative Research Center. „This cab transports the drugs to their destination in the body and brings them to their precise effect there.“