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24.06.2026 15:06

Viruses under stress: how viral shells change shape as they dry out

Thomas Reintjes Presse- und Öffentlichkeitsarbeit
European XFEL GmbH

When viruses travel through the air in tiny droplets, they can quickly start to dry out. Yet many viruses remain infectious after rehydration—something that is still not fully understood. Now, an international team of researchers have directly observed at the European XFEL how the protein shells of viruses can change shape during dehydration, offering new clues to viral resilience and opening new possibilities for virology research. The results, published in Light: Science & Applications, lay the groundwork for potential applications in virology and public health, and can for instance help developing antiviral strategies.

At the SPB/SFX instrument of the European XFEL, Abhishek Mall from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg (MPSD), and his colleagues explored the structural dynamics of the protein shells—called capsids—that enclose the genetic material of viruses. Specifically, they examined the behaviour of capsids of the bacteriophage MS2 under conditions of dehydration. MS2 is an icosahedral, i.e. shaped by 20 triangular surfaces that form a sphere, single-stranded RNA virus that infects the bacterium Escherichia coli, and is widely used as a model system in virology.

The capsid’s design is critical for protecting the viral genome and helping the virus interact with host cells. However, viruses are often confronted with environments that challenge their structural integrity, for example through dehydration. Theoretical studies have long suggested that capsids may undergo low-energy “buckling transitions”—sudden changes in shape—to adapt to such stresses, but direct experimental evidence has been lacking.

The work of Abhishek Mall and his colleagues from research institutions in Germany, Sweden, the United Kingdom, Australia, Singapore, and the United States fills that gap. They very finely sprayed a liquid containing the viruses into an extremely low-humidity sample chamber, creating an aerosol. The droplets travel for a little more than a second, while some of the surrounding liquid evaporates, mimicking a natural dehydration process. At some point they meet the XFEL beam, which essentially takes a snapshot of the capsid. “We used single-particle imaging to investigate the morphological changes in viral capsids during aerosolization”, Abhishek Mall says. He and his colleagues collected diffraction patterns from hundreds of thousands of individual MS2 particles.

As co-author Kartik Ayyer, group leader at the MPSD, explains, the team initially aimed to capture only the final, dried state. But the experiment turned into something more powerful, because it produced many particles at different points along the drying process. “This was actually a good thing”, Ayyer says. “It allowed us to reconstruct a trajectory of structural change by sorting the snapshots from fully hydrated to fully dried and anything in-between.”

A surprising asymmetry

One of the key findings of the study was the observation of buckling in the MS2 capsids as they transitioned from a hydrated to a dehydrated state. The buckling can be compared to a thin plastic bottle that under negative pressure bulges in in certain spots as opposed to shrinking uniformly. The researchers observed that in the hydrated state, the capsids exhibited near-perfect icosahedral symmetry, as determined by cryo-electron microscopy. “However, as dehydration progressed, the capsids adopted more compact conformations, with significant deviations from icosahedral symmetry”, describes Mall.

Importantly, the changes were not uniform across the capsid. Instead, the transition appeared to happen locally, with some regions changing before others. “This finding is particularly significant as it provides direct experimental evidence for a mechanism that had previously been only theoretically predicted”, adds Richard Bean, leading scientist at the SPB/SFX instrument.

The observation also challenged a common assumption about viruses. “Many people had the impression that this capsule is like a rigid container. And this is absolutely not what we saw”, Ayyer explains. Instead, the capsid appears mechanically adaptable to changing conditions.

Molecular “trigger” for buckling

The study also explored the molecular mechanisms underlying these morphological changes. “Molecular dynamics simulations revealed that a flexible segment of the protein called FG loop plays a crucial role in the observed structural transformations”, states Mall. “These movements led to the contraction of the FG loops around the three-fold and five-fold pores of the capsid, resulting in a more compact structure.” The researchers assume that this contraction is driven by the loss of stabilizing water molecules, which are critical for maintaining the extended conformation of the FG loops. This localized destabilization probably acts as a protective mechanism, potentially reducing how exposed the viral genome is during drying.

New application of machine learning

Crucial to the study was its methodological innovation. By integrating single-particle imaging (SPI) with advanced machine learning techniques, such as β-variational autoencoders (β-VAEs), the researchers were able to analyse structural heterogeneity across a large data set of diffraction patterns. “The use of β-VAEs allowed for the classification of particles into a continuous latent space, capturing variations in size and shape with remarkable precision”, explains Mall. This approach not only identified the endpoints of the structural transition—from hydrated to dehydrated states—but also mapped the intermediate conformations that bridged these states. “Such detailed analysis would have been impossible with traditional ensemble-averaged methods”, Bean adds. He continues: “The ability to capture and analyse the structural landscape of viral capsids in real time is a significant advancement in structural biology via single particle imaging. The methods employed in this study can be extended to other biomolecular systems, providing a powerful tool for investigating dynamic processes that are otherwise challenging to study.”

How viruses survive in air

The structural adaptability observed in the capsids provides fundamental insight into how viruses may survive environmental stresses. This knowledge is particularly relevant regarding viruses transmitted by aerosols, including many pathogens that affect humans. “By elucidating the mechanisms that enable viral resilience, the work of Abhishek Mall and his colleagues lays the groundwork for potential applications in virology and public health, for instance, to develop antiviral strategies”, says Sakura Pascarelli, Scientific Director at European XFEL. The findings shed light on a critical aspect of viral survival. “The results not only advance our understanding of viral mechanics but also open new avenues for research and innovation in virology and structural biology”, underlines Pascarelli.

Further studies are planned to investigate the observed behaviour under more realistic conditions. “In this experiment, we used a very clean liquid, that completely evaporates”, Ayyer cautions. “Real saliva has salts, for instance, that don’t evaporate, as well as proteins. The next step is to use proxies for saliva, so we can determine what role the changing shape of the viral shell plays in real life.”

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Wissenschaftliche Ansprechpartner:

Kartik Ayyer
+49 40 8998-88150
kartik.ayyer@mpsd.mpg.de

Richard Bean
+49-40-8998-6843
richard.bean@xfel.eu

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Originalpublikation:

https://doi.org/10.1038/s41377-026-02262-0

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Weitere Informationen:

https://www.xfel.eu/news_and_events/news/index_eng.html?openDirectAnchor=3043&am...

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Model of the structurally transformed capsid at 6.1 nm resolution
Quelle: MPSD
Copyright: MPSD

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Merkmale dieser Pressemitteilung:
Journalisten
Biologie, Chemie, Medizin, Physik / Astronomie, Werkstoffwissenschaften
überregional
Forschungsergebnisse
Englisch

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