17-Sep-2021 - Technische Universität München

Machine learning assisted structure analysis reveals SARS-CoV-2 virus tactics

The proteins of Covid-19

The proteins of SARS-CoV-2 play key roles in how the virus manages to evade immune defense and replicate itself in patients’ cells. An international research team – with significant contribution from the Technical University of Munich (TUM) – has now compiled the most detailed view of the virus' protein structures available to date. The analysis employing artificial intelligence methods has revealed surprising findings.

How does the SARS-CoV-2 virus manage to evade immune defense and replicate itself in patients suffering from COVID-19? To shed light on this question, an international research team has assembled the most comprehensive view to date on the precise, three-dimensional shape of each SARS-CoV-2 protein – including the well-known spike protein.

To assemble this map, the team used high-throughput machine learning, an approach that enabled them to predict structural states likely to occur in coronavirus proteins, based on states that have been seen in related proteins. The final map consists of 2,060 atomic-resolution 3D models involving the coronavirus’s 27 proteins. All structural models are freely available through the Aquaria-COVID resource.

“This provides an unprecedented wealth of detail that will help researchers better understand the molecular mechanisms that cause COVID-19, and will help in developing therapies to fight the pandemic, for example, by identifying potential new targets for future treatments or vaccines,” says Burkhard Rost, professor of bioinformatics at the Technical University of Munich.

The structural coverage map – key to a wealth of knowledge

A second part of the study used a complementary approach, known as human-in-the-loop machine learning, to create a novel, visual interface that summarizes everything currently known – and not known – about the shape of SARS-CoV-2 proteins.

The visual interface, called a structural coverage map, can also be used as a navigation aid for researchers, helping them find and use structural models that relate to specific research questions. And these models have already revealed several vital clues into how coronaviruses are able to take over our cells.

How coronaviruses take over our cells

Using their machine learning approaches, the team was able to identify three coronavirus proteins (NSP3, NSP13, and NSP16) that ‘mimic’ human proteins, successfully fooling a host cell into believing that they are native proteins operating in the best interest of the cell. 

The modelling also revealed five coronavirus proteins (NSP1, NSP3, spike glycoprotein, envelope protein, and ORF9b protein) that the researchers say ‘hijack’ or disrupt processes in human cells, thereby helping the virus take control, complete its life cycle and spread to other cells.

Understanding how the virus operates – and how to stop it

“In analyzing these structural models, we also found new clues into precisely how the virus copies its own genome – which is the central process that allows the virus to spread rapidly in any person unlucky enough to become infected,” says Burkhard Rost. “The insights from our study take us closer to understanding how the virus operates, and what we can do to stop it.”

“The longer the virus circulates, the more chances it has to mutate and form new variants such as the Delta strain,” says Professor O’Donoghue, the lead author of the study from the Garvan Institute in Sydney. “Our resource will help researchers understand how new strains of the virus differ from each other – a piece of the puzzle that we hope will help in dealing with new variants as they emerge.”

Facts, background information, dossiers

  • SARS-CoV-2
  • coronaviruses
  • Covid-19
  • proteins
  • structural analysis
  • machine-learning
  • artificial intelligence
  • protein analytics

More about TU München

  • News

    New approach identifies T cells in Covid-19 patients

    T cells play a decisive role in fighting the coronavirus and preventing infected individuals from becoming seriously ill. They identify and fight the virus directly within the infected cells. A team of researchers working in Munich have produced a precise profile of the T cells that respond ... more

    The virus trap

    To date, there are no effective antidotes against most virus infections. An interdisciplinary research team at the Technical University of Munich (TUM) has now developed a new approach: they engulf and neutralize viruses with nano-capsules tailored from genetic material using the DNA origam ... more

    Versatile and reliable SARS-CoV-2 antibody assay

    During the continued progression of the Corona pandemic, rapid, inexpensive, and reliable tests will become increasingly important to determine whether people have the associated antibodies – either through infection or vaccination. Researchers at the Technical University of Munich (TUM) ha ... more

  • q&more articles

    Biobased raw material flows of the future

    Anthropogenic climate change and the rising world population, in combination with increasing urbanization, poses global challenges to our societies that can only be solved by technological advancement. The direct biotechnological use of greenhouse gases, including residual biomass flows fro ... more

    Taste and aroma boost in the mouth

    The food trend towards healthy snacks is continuing. Snacks made from freeze-dried fruit meet consumer expectations of modern and high-quality food. However, freeze drying of whole fruits requires long drying times and substantially reduces sensorial quality, which is unappealing to consumers. more

    Diet, gut microbiota and host lipid metabolism

    Nature provides an enormous diversity of lipid molecules that originate from various pathways. Fatty acids are key modules for various lipids, including cell membrane lipids such as phospholipids or triacylglycerols, which are the major components of lipid droplets. Excess lipids or defects ... more

  • Authors

    Prof. Dr. Thomas Brück

    Thomas Brück, born in 1972, obtained his B.Sc. in chemistry, biochemistry and management science from Keele University, Stoke on Trent. Additionally, he holds an M.Sc. in molecular medicine from the same institution. In 2002, Thomas obtained his Ph.D. in Protein Biochemistry from Imperial C ... more

    Dr. Norbert Mehlmer

    Norbert Mehlmer, born in 1977, studied biology at the University of Salzburg and wrote his diploma thesis at the Max Planck Institute for Molecular Genetics in Berlin. He earned his doctorate in genetics/microbiology at the Max F. Perutz Laboratories (MFPL) of the University of Vienna. Subs ... more

    Dr. Mahmoud Masri

    Mahmoud Masri accomplished his studies in Applied Chemistry at the University of Damascus and received his Master in 2010. He has been working as Quality Assurance Manager for five years. In 2019, he obtained his doctoral degree in biotechnology at the Technical University of Munich (TUM) w ... more

q&more – the networking platform for quality excellence in lab and process

The q&more concept is to increase the visibility of recent research and innovative solutions, and support the exchange of knowledge. In the broad spectrum of subjects covered, the focus is on achieving maximum quality in highly innovative sectors. As a modern knowledge platform, q&more offers market participants one-of-a-kind networking opportunities. Cutting-edge research is presented by authors of international repute. Attractively presented in a high-quality context, and published in German and English, the original articles introduce new concepts and highlight unconventional solution strategies.

> more about q&more

q&more is supported by: