Why viruses like Herpes and Zika will need to be reclassified, and its impact on biotechnology

New research reveals that the way in which viruses have been perceived in terms of architecture will have to be reorganized, as they are actually structured in a much larger number of models than previously understood. The results could have a significant impact on how they are categorized, our understanding of how they are formed, evolve, and infect hosts, as well as strategies for identifying ways to design vaccines to target them.

In the 1950s and 1960s, as scientists began to obtain high resolution images of viruses, they discovered the detailed structure of the capsid, an outer protective layer of multiple copies of the same protein that protects the genetic material from the virus. . The majority of viruses have typically spherical capsids and display icosahedral symmetry, such as a 20-sided die.

The shell of the capsid is what protects them, and when scientists discovered their structure, they proposed that the capsids could have different sizes and contain different amounts of genome, and thus they could infect hosts differently.

Why is it important

When designing drugs to target viruses, scientists can now take into account their different structural forms to improve their effectiveness.

Two researchers studying the structures of viruses: Antoni Luque, theoretical biophysicist at San Diego State University and member of his Viral Information Institute, and Reidun Twarock, biologist mathematician at the University of York, UK, and member York's Cross. Center for Systems Analysis, show that many viruses have been misclassified for 60 years, including common viruses such as Herpes simplex and Zika.

Indeed, despite the structural images from cryogenic microscopy, we did not have the mathematical description of many different virus architectures.

"We have discovered six new ways that proteins can organize to form icosahedral capsid shells," said Luque. "Thus, many viruses do not only embrace both widely understood capsid architectures, but there are now at least eight ways to design their icosahedral capsids."

They used a generalization of the quasiequivalence principle to see how proteins can wrap an icosahedral capsid.

Their study, which will be published in Nature Communications On Friday, September 27th, viruses belonging to the same structural line, based on the protein of which they are composed, adopt coherent presentations of the icosahedral capsid, thus offering a new approach for studying the evolution of the virus.

Biotechnological applications

Structural biologists can now take this information and reclassify the structure of viruses, which will help unravel the molecular and evolutionary relationships between different viruses.

It will also provide a guide for the design of new molecular containers for nanotechnology and biotechnology applications, and help scientists identify specific strategies for targeting protein assembly in the capsid. This could eventually lead to a more systematic approach to the development of antiviral vaccines.

"We can use this discovery to target both the assembly and stability of the capsid, either to prevent the formation of the virus when it infects the host cell, or to separate it after its formation," he said. said Luque. "This could facilitate the characterization and identification of antiviral targets for viruses sharing the same icosahedral arrangement."

This new framework supports previously aberrant viruses, provides new predictions on viral capsid architectures, and has identified common geometric patterns among evolutionarily-related evolutionary viruses that infect everyone from humans to bacteria.

Twarock said the new plans also provided "a new perspective on viral evolution, suggesting new avenues for larger and more complex viruses to evolve from simple viruses to evolving time scales."

Architectural applications

Geometries could also be used in new architectural designs in buildings and construction.

Since the 1960s, these viral capsids have been classified according to the geometric framework introduced by structural biologist Donald Caspar and biophysicist Aaron Klug, inspired by the geodesic domes designed by renowned architect R. Buckminster Fuller. However, with the advance of molecular imaging techniques, an increasing number of reconstructions of 3D viral capsids integrating viruses such as herpes or Zika virus have fallen from this classic geometric framework.

"This study introduces a more general framework than the classic Caspar-Klug construction and is based on the conservation of local peaks formed by the proteins that interact in the capsid," explained Luque. "This approach has led to the discovery of six new types of icosahedral capsid layouts, while recovering the two classic Caspar-Klug presentations based on Goldberg's polyhedra and geodesics."

"Structural enigmas in virology resolved according to a principle of global icosahedral conception" are published in Nature Communications.