Futuris explores how researchers are using tools from the field of physics and other scientific disciplines to help better understand COVID-19.
In Hamburg scientists are studying the elusive protein structures that enable coronaviruses, including SARS-CoV-2, to take hold. They are trying to find out how they are able to replicate so rapidly inside human cells.
The more they know about these proteins, the better chance there will be to develop treatments and vaccines. The first step seeks to produce proteins in different cell types. Researchers say the challenge is huge.
"The proteins have to be produced in different cell types and some proteins can resist this process, explains Boris Krichel, a virologist at Heinrich Pette Institute, adding: "That's always a little difficult. These proteins then become too large or are modified. This is why you have to take certain cell types in order to get them in a way they can be studied.
Despite the obstacles, scientists say the work they are doing is crucial.
“The job of these proteins is to replicate the viral genome. If we know how the individual parts function and how they are put together, then we can use this knowledge to develop drugs that specifically stop these individual proteins,” says Krichel.
Mapping mutations with mass spectrometry
Once produced, the proteins are analysed using mass spectrometry. The resulting spectra reveal the chemical identity or the structure of a given protein.
"First I can use the mass spectrometer to measure the protein and afterwards a substance that possibly binds to the protein. So first of all, I measure the protein alone, then the protein with the substance. By using the mass spectrometer I can see whether these two combine and I can also analyse how strong this bond is. And that is important for drug design or drug development,” says Kira Schamoni, a Molecular Biologist at the Heinrich Pette Institute.
These types of proteins are routinely studied with tools like crystallography or electron microscopy. But the researchers see big advantages in mass spectrometry.
"With mass spectrometry we can map the different states in which a protein exists simultaneously," explains Charlotte Uetrecht, a structural virologist and group leader at the Heinrich Pette Institute. She adds: "We can see if it has been modified and if it can take on other states due to this modification. And within the framework of this project, we are now trying to develop mass spectrometry that not only complements electron microscopy or other structural techniques, but (that) can also achieve a similar level of detail in terms of resolution.”
"I can use a mass spectrometer to measure the native state of a protein. That means I can really measure the dynamics of the protein. I can’t necessarily do this with other methods of structural biology,” explains Schamoni.
Scientists taking part in this European Research Council project started their work on mass spectrometry and coronavirus protein structures back in 2018. Their research has turned out to be extremely useful in understanding how the SARS-CoV-2 virus replicates. It should also eventually help develop more tools to fight the pandemic.
"Coronaviruses are generally a challenge due to the size of their genetic material. We started the project with SARS-coronaviruses and related viruses, and we are now trying to extend it to SARS-CoV-2. The two viruses SARS-CoV and SARS-CoV-2 are very similar. So the challenges are the same,” says Uetrecht.
"Working for everyone"
The project is just one of the many currently being backed by the EU. Other initiatives to fight the pandemic include research to develop new vaccines, treatments and testing. The European Commission’s chief for research and innovation Mariya Gabriel says its part of a large-scale effort to improve knowledge to deliver results.
“Europe makes up 7 percent of the world’s population, but accounts for 20 percent of world’s investment in research and innovation and 21 percent of the highest ranking scientific papers. We must continue to support the European Research Council, so that it is able to maintain this ability to produce research that is driven by curiosity, that is cutting edge, in order to anticipate what will happen next," Gabriel told Euronews.
Such research will soon come under the umbrella of "Horizon Europe”. The ambitious €100 billion programme seeks to address global challenges, while at the same time promoting science, innovation and European competitiveness.
The Commissioner for Research and Innovation added: "We have two main challenges. The first one is to keep on investing huge amounts in research and innovation, as the crisis has shown to what extent they are critical if we want to offer solutions that will allow our economies and societies to be better prepared for the next crisis. The second challenge is that of cooperation and coordination, because we are all well aware: the virus does not respect borders. It’s important to keep focusing on this, to have international cooperation; global coordination, so that we can say, thanks to European Union leadership, we are working for everyone."
Back in Hamburg, researchers say their technique is not only limited to viruses or coronaviruses - it can also be used on complex biological proteins.
"If we think of a machine, for example a car, if we only look at it from the outside or only hear it, we will not know how it works. To do this, you have to look at the engine in detail, watch it at work, perhaps even take it apart and look at how the individual components function. And that is exactly what structural biology is trying to do: to look at the individual proteins, to observe their complexity and see the entire machine at work," says Uetrecht.
Researchers say they are satisfied with what has been achieved so far, but insist more work will be needed if they are to go beyond the current technological boundaries. Their project is scheduled to continue until the end of 2022.