New study on viruses could help design engineered nano-shells used in drug delivery

Viruses are small disease-causing parasites with the potential to infect all life forms.

Although they have been analyzed well, several mysteries still exist. One of these is how a spherical virus manages to circumvent energy barriers to develop symmetric shells.

Photo shows, from left to right, Sanaz Panahandeh, Roya Zandi, and Siyu Li. Image Credit: Zandi lab, UC Riverside.

Led by physicist Roya Zandi from the University of California, Riverside, a group of researchers has been able to solve this mystery. In an article published in ACS Nano, the researchers report that a combined effect of energies at the molecular level renders the formation of a shell feasible.

Biomedical attempts to inhibit viral replication and infection could be enabled by gaining insights into the factors that play a role in viral assembly.

Better insights into the formation of viral shells—natural nano-containers—is highly significant to material scientists, and is a critical stage in the development of engineered nano-shells acting as vehicles for delivering drugs to particular targets in the body.

Zandi and her colleagues investigated the role of elastic energy and protein concentration in the self-organization of proteins on the curved shell surface to perceive how a virus circumvents several energy barriers.

Understanding the combined effect of elastic energy, genome-protein interaction, and protein concentration in the viral assembly constitutes the breakthrough of our work. Our study shows that if a messy shell forms because of the high protein concentration or strong attractive interaction, then, as the shell grows larger, the cost of elastic energy becomes so high that several bonds can get broken, resulting in the disassembly and subsequent reassembly of a symmetric shell.”

Zandi, Professor, Department of Physics and Astronomy, UC Riverside

What is a virus?

A virus is the most basic physical object in biology that comprises a protein shell known as the capsid for protecting its nucleic acid genome—DNA or RNA.

Viruses can be considered as mobile containers of DNA or RNA that introduce their genetic material into living cells. They then take over the reproductive machinery of the cells to reproduce their own capsid and genome.

The formation of the capsid is one of the most vital steps during viral infection. Although the shape of the capsid can be conical or cylindrical, it more commonly assumes an icosahedral structure, similar to that of a soccer ball.

An icosahedron is a geometrical structure with 30 sides, 20 faces, and 12 vertices. An example of one type of icosahedron, known as a truncated icosahedron, is an official soccer ball. It has 32 panels cut into the shape of 12 pentagons and 20 hexagons, where the hexagons separate the pentagons from each other.

Since viruses are extremely small, measuring in nanometers (one nanometer equals one-billionth of a meter), it is difficult to understand viral assembly.

Moreover, the assembly occurs very quickly, usually in a few milliseconds, where one millisecond is one-thousandth of a second. Theoretical studies and simulations are essential to understand the way a virus grows.

A viral shell is highly symmetric. If one pentagonal defect forms in the wrong location, it breaks down the symmetry. Despite this sensitivity, viral shells are often assembled into well-defined symmetric structures.”

Zandi, Professor, Department of Physics and Astronomy, UC Riverside

Nano vehicles

According to Zandi, there is a lack of proper understanding of the virus assembly process is due to the dearth of experimental data. The new study identified the capsid proteins’ elastic properties and that the attractive interaction between them works to form highly symmetric configurations that are very stable energetically.

By fine-tuning these parameters, we can control the final structure and stability of viral capsids. These viral capsids can be used as nano-containers for transporting drugs as cargo to specific targets. What makes them highly promising for drug delivery and gene delivery purposes is that they are stable, have a high uptake efficiency, and have low toxicity.”

Zandi, Professor, Department of Physics and Astronomy, UC Riverside

A few experimental teams have already joined hands with pharmaceutical companies to develop drugs that inhibit or interrupt viral assembly. Zandi’s lab has collaborated with international collaborators to develop simulations to gain better insights into virus assembly.

“Understanding the factors that affect the stability of the final viral structures can make drug delivery processes more controllable,” Zandi added.