Geometric architecture of viruses

Abstract

In the current SARS-CoV-2 disease (COVID-19) pandemic, the structural understanding of new emerging viruses in relation to developing effective treatment and interventions are very necessary. Viruses present remarkable differences in geometric shapes, sizes, molecular compositions and organizations. A detailed structural knowledge of a virion is essential for understanding the mechanisms of capsid assembly/disassembly, antigenicity, cell-receptor interaction, and designing therapeutic strategies. X-ray crystallography, cryo-electron microscopy and molecular simulations have elucidated atomic-level structure of several viruses. In view of this, a recently determined crystal structure of SARS-CoV-2 nucleocapsid has revealed its architecture and self-assembly very similar to that of the SARS-CoV-1 and the Middle-East respiratory syndrome virus (MERS-CoV). In structure determination, capsid symmetry is an important factor greatly contributing to its stability and balance between the packaged genome and envelope. Since the capsid protein subunits are asymmetrical, the maximum number of inter-subunit interactions can be established only when they are arranged symmetrically. Therefore, a stable capsid must be in a perfect symmetry and lowest possible free-energy. Isometric virions are spherical but geometrically icosahedrons as compared to complex virions that are both isometric and helical. Enveloped icosahedral or helical viruses are very common in animals but rare in plants and bacteria. Icosahedral capsids are defined by triangulation number (T = 1, 3, 4, 13, etc.), i.e., the identical equilateral-triangles formed of subunits. Biologically significant defective capsids with or without nucleic acids are common in enveloped alpha-, flavi- and hepadnaviruses. The self-assembling, stable and non-infectious virus-like particles have been widely exploited as vaccine candidates and therapeutic molecules delivery vehicles.

Keywords: Virus; Virion; Capsid structure; Icosahedron; Triangulation number

Core tip: A detailed structural knowledge of a pathogenic virus is essential for understanding the mechanisms of capsid assembly, antigenicity, cell receptor interaction, and designing therapeutic strategies. X-ray crystallography, cryo-electron microscopy and molecular simulations have elucidated atomic-level structures of several viruses. Notably, a recently determined crystal structure of SARS-CoV-2 capsid has revealed its close similarity to that of SARS-CoV-1 and MERS-CoV. Capsid symmetry greatly contributes to virion stability and balance between genome. Enveloped icosahedral viruses are very common in animals, and rare in plants. Several of self-assembled, stable and non-infectious virus-like particles have been widely exploited as vaccine candidates and therapeutic molecules delivery vehicles.