Researchers reveal secrets of smallpox viruses and hope for success of future therapy
Kyiv • UNN
Researchers have uncovered the secrets of smallpox virus architecture using cryo-electron microscopy and molecular modeling, finding the key protein A10 that determines the structure of the viral core, and hoping that this will help in the future development of antiviral treatments.
A team of researchers from the Austrian Institute of Science and Technology (ISTA) has unraveled the secrets of the poxvirus core architecture. This is especially relevant in light of the emergence of monkeypox cases in different countries. The results of the new study may become the basis for new drugs.
This is reported by UNN with reference to Nature Structural & Molecular Biology.
Details
A team of scientists from the Austrian Institute of Science and Technology (ISTA) has recognized a number of interesting patterns in the architecture of the poxvirus core by combining various cryo-electron microscopy techniques with molecular modeling.
Poxviruses can only be infectious when their viral core is fully formed. Therefore, it was important to find out what the "poxvirus core", the common core of clinically relevant smallpox viruses, consists of, and how its individual components are composed and how they work. This was stated by Florian Schur, associate professor at ISTA and lead author of the study. study, description of the problem.
Schur and his team are currently investigating the missing link: a protein called A10. The ISTA team has discovered that A10 is one of the basic building blocks of the poxvirus core, which is one of the central building blocks common to all clinically relevant poxviruses.
The team focused on calculating predictive models of the main candidate proteins using the now well-known AI-based molecular modeling tool AlphaFold.
We have integrated many of the most advanced cryo-EM techniques available today with AlphaFold molecular modeling. (...) This has given us for the first time a detailed global view of the poxvirus core, the "vault" or "bioreactor" within the virus that surrounds the viral genome and releases it into infected cells
Using electron cryotomography, researchers can reconstruct 3D volumes of a biological sample as large as an entire virus.
The researchers were able to fit AlphaFold models to the observed shapes and identify the molecules that make up the core of the poxvirus.
Among them, the central candidate protein A10 stood out as one of the main components.
We found that A10 defines key structural elements of the poxvirus core
Researchers have developed protocols to purify the complete viral core while optimizing these samples for structural studies.
It was extremely difficult to study these viral cores structurally. But fortunately, our persistence and optimism paid off
Scientists now hope for future progress in creating drugs that prevent the smallpox virus core from assembling or even cause it to break down and not release viral DNA during infection.
Today's findings can provide a knowledge platform for future therapies.
Ultimately, basic research on viruses, such as the one conducted here, allows us to be better prepared for possible future virus outbreaks
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