Single crystal X-ray diffraction analysis of virus structure and its applications in the development of pharmaceutical agents

• Published in: Crystallography reviews Vol. 21; no. 1-2; pp. 103 - 121
• Main Author: Luo, Ming
• Format: Journal Article
• Language: English
• Published: Abingdon Taylor & Francis 02.01.2015; Taylor & Francis Ltd
• Subjects: Antiviral drugs; conserved protein fold; Crystal structure; Crystallography; electron density averaging; icosahedral layout; non-crystallographic symmetry; rotation function; Single crystals; Symmetry; synchrotron sources; viral capsid; Viruses
• ISSN: 0889-311X; 1476-3508
• DOI: 10.1080/0889311X.2014.957281

Virus particles are among the biological subjects that were first found to form single crystals. Their atomic structures were solved when X-ray sources became stronger in intensity. Virus crystals have large unit cell dimensions and are generally sensitive to X-ray radiation. However, the high symmetry of virus particles allows the crystal structure to be solved by non-crystallographic symmetry averaging of electron densities using only the Bragg reflection intensities. Virus crystal structures have expanded our understanding of the principles of virus assembly, recognition of the host receptor, and virus escape from the surveillance of the human immune system. Spherical virus particles are assembled from common capsid subunits and whose layout follows icosahedral symmetry. Interatomic interactions among the capsid protein subunits, especially through their extended termini and loops, stabilize the viral protein shell to encapsulate the viral genome. Conserved folds are found in the protein capsid subunits, such as the β-barrel fold initially observed in the small RNA viruses. These various viral molecular properties and overall layout have been exploited in the design of antiviral pharmaceutical compounds.