Understanding Self-Assembly in Viral Capsids

In a study published today in eLife, international researchers investigated the conditions that control self-assembly of the viral protein shell (capsid). The study highlights factors that can disrupt capsid self-assembly, which would prevent viruses from replicating. Manipulating these factors could allow scientists to induce misassembly in viral capsids, which could be an approach to combat viral infections.

Viruses are formed by a chain of the nucleic acids that are encased in a capsid, which is made, in the simplest cases, from multiple copies of a single protein. These capsids have a very precise architecture, allowing them to protect, carry, and deliver viruses to their host.

“During self-assembly, a favorable binding energy competes with the energetic cost of the growing edge and the elastic stresses generated by the curvature of the capsid,” explains first author Carlos Mendoza of Universidad Nacional Autónoma de México. “As a result, incomplete structures such as open capsids and cylindrical or ribbon-shaped shells may emerge during assembly, preventing the successful replication of viruses.”

Mendoza says that previous studies of self-assembly in capsids have mostly focused on the templated growth on the surface of a sphere or else on the optimal shape of the resulting capsid. They have not considered the potential importance of other “ingredients” on capsid stability and formation, such as the line tension, the chemical potential difference, or the preferred curvature.

To address this gap, the team analyzed the conditions and mechanisms leading to the misassembly of empty viral capsids, taking into account all these “ingredients.” Their analyses revealed that capsid self-assembly depends on three factors that can be manipulated to cause the formation of non-spherical and open shells.

“We found that the outcome of self-assembly can be recast into a universal phase diagram, a type of chart that highlights the conditions for successful viral assembly and the key factors that prevent it,” says senior author David Reguera of Universitat de Barcelona, Spain. “Our findings advance our understanding of the physics controlling the assembly of curved shells and explain why viruses with high mechanical resistance cannot be assembled directly and need a maturation process to stiffen the capsid and become infective.”

The authors add that their results can only be applied directly to icosahedral viruses—including papillomavirus, polyomavirus, and poliovirus—and not to viruses with helical nucleocapsids like SARS-CoV-2.