Study decrypts the key elements for the assembly of a large virus; understand that his training could contain the spread of viruses – ScienceDaily

The formation of a capsid is one of the most crucial steps of the viral infection process. If the virus is small, the capsid is formed spontaneously. However, larger spherical viruses, such as herpes simplex virus or infectious bursal disease virus, require the help of naturally produced "scaffold proteins", which serve as a model for the formation of the disease. capsid. The way these large viral shells fit into very symmetrical structures is not well understood.

A team of physicists and a virologist, led by a scientist from the University of California, Riverside, published a research article in the Proceedings of the National Academy of Sciences explaining how big shells of viruses are formed. Their work can also be used to explain the formation of large spherical crystals in nature.

This understanding can help researchers stop the formation of viruses, causing the spread of viral diseases.

Building on a theory called the continuum elasticity theory, researchers studied the growth of large spherical capsids. They showed that the template guided the formation of the protein subunits of the capsid – the various constitutive elements of the shell – irreproachably and finally gave a stable and highly symmetrical icosahedral structure.

"As the spherical structure develops, we see deep potential wells – or affinities – at mathematically specified locations that will later become the peaks of the icosahedral structure," said Roya Zandi, Professor, Department of Physics. and astronomy University led the research project. "In the absence of this matrix provided by scaffold proteins, protein subunits often bademble into smaller and less stable structures."

The study includes computer simulations and complex mathematics, especially topology, which is the mathematical study of the properties of a geometrical figure or solid that are not modified by stretching or bending. He explains in a fundamental way the role played by the mechanical properties of building blocks and scaffold proteins in the formation of capsids. For large capsids to have stable icosahedral structures, the protein subunits must have specific physical properties. In addition, an interaction between protein subunits and a model is necessary, say the researchers.

An icosahedron is a geometric structure with 12 vertices, 20 faces and 30 sides. An official football is a kind of icosahedron, called truncated icosahedron; it has 32 panels cut in the shape of 20 hexagons and 12 pentagons. It has 60 vertices and 90 edges. Pentagons are separated from each other by hexagons. All icosahedral structures, regardless of size, should have only 12 pentagons.

Zandi explained an icosahedron by invoking Thomson's problem, according to which point charges placed on the surface of a sphere unit would minimize the total energy of the system. Solutions to the problem place each point so that its closest neighbors are as far apart as possible.

"If you have a spherical conductor and you place 12 electrons there, they will want to be as far apart as possible," she said. "They end up on the tops of an icosahedron.Because of this knowledge, when a virus shell develops, then, on the basis of the theory of elasticity, you will need to 39, at least 12 defective points, called revelations Imagine if you had to wrap a sheet of paper around a sphere, you would have to fold the paper in some places to give it the spherical shape. can not be avoided If you had to create a spherical shell using small triangles, would need to make 12 pentagons.Without 12 pentagons, a spherical shape is not possible. "

Zandi pointed out that in order to attack viruses more effectively, a good understanding of their form is needed, which can inform researchers of the best ways to interrupt their training and thus contain the spread of viral diseases.

"When a virus is large, how do protein subunits know how to prepare to form the most stable shell possible – an icosahedral shell?" she added. "Where Should the First Disclosure Occur and the Next, How Can Thousands of Protein Subunits Unite to Form Icosahedral Structures with Such Accuracy and Symmetry?" And What Is the Role of Proteins on Why stable shells can not be formed without scaffolding proteins These questions have guided our research. "

Zandi explained that each protein subunit has bending energy, which means that one subunit prefers to meet another subunit at a certain angle. For a small icosahedral structure, this angle is small and acute. But to form a large icosahedral or capsid structure, this angle is large and obtuse and requires the badistance provided by the scaffolding proteins. Without this badistance, the protein subunits would form a long endless tube because this effort requires less energy.

"We now show that this trend is thwarted by the scaffolding proteins, which cause the protein subunits to bend slightly, curl and form 12 pentagons, which then leads to the formation of the subunits. an icosahedral structure, "said Zandi. "Our study shows that without this scaffold, it is impossible to form a large, highly stable icosahedral shell."

Viruses are the best nano-containers, Zandi said. They can be used to administer drugs to specific targets in the body because they are particularly able to reach cells. For example, viruses can be used to transport cargoes, such as genomes and drugs, for therapeutic purposes to cancer cells.

"Anti-badembly drugs may be more effective than other drugs because the viral form is particularly sensitive to mutations at specific badembly interfaces," Zandi said. "Indeed, small molecules have recently been designed to prohibit the replication of some viruses by similar mechanisms."

Viruses do not breathe, do not metabolize, and do not grow. But they breed. The simplest virus has a shell of 60 protein subunits. Three asymmetric subunit proteins occupy each triangular face and the 60 subunits are equivalent. For complex viruses, the number of subunits is a multiple of 60.

The study was funded by a grant from the National Science Foundation.

Zandi was joined in the search by Siyu Li of UCR; virologist Polly Roy of the London School of Hygiene and Tropical Medicine, United Kingdom; and Alex Travesset from Iowa State University. Li, a graduate student in Zandi's lab, is the first author of the research paper.