Viruses require a host cell to replicate and most on a protein shell called capsid to protect their infective genome. Capsids are built from multiple copies of the major capsid protein (MCP) and, in some cases they include additional copies of minor, auxiliary, or reinforcement proteins. The interactive surfaces of the capsid proteins have been selected to assembly viral capsids spontaneously once a sufficient capsid protein concentrations are achived. This strategy has allowed viruses to encode a relatively small fraction of their genomie to generate a shell that contains a volume capable of enclosing a significantly larger amount of genomic information. This extraordinary nanotechnoligal feat is probably the underlying reason of the success of viruses in the planet, being the most abundant and playing key roles in the biogeochemistry of Earth. However, our understanding of the different capsid architectures and their relative advantages and roles beyond genome storage remains mostly unexplored. One important gap in the field is the lack of a rigurous method to compare and classify capsid anatomies.
The majority of viral capsids adopt icosahedral symmetry (Montiel-Garcia et al. 2021). Icosahedral capsids represent approximately 90% of the viruses observed in the environment (Ackermann and Prangishvili;(Brum et al. 2013)[#Brum2013ISMEJ]), and more than 60% of the classified taxonomic families produced icosahedral capsids (Krupovic and Koonin 2017). There are also several geometrical theories that facilitate the classification of icosahedrla structures. Thus, focusing on establishing standard protocols to characterize the anatomy of icosahedral capsids would cover already a vast amount of viruses in the world. At the same time, the approaches developed for this type of capsids would provide a guide on how to characterize the capsid anatomy of other capsid types.
Traditionally, icosahedral capsids have been classified using the quasiequivalence theory of icosahedral capsids introduced in Caspar and Klug 1962. The most important advantage of this theory was the clear prediction of different icosahedral capsids formed by different number of proteins. The capsids displayed a stoichomery proportional to sixty proteins, 60T. The index T was integer derived from the constraint of having icosahedral symmetry and followed the Diophantien equation T(h,k) = h$^2$ + hk + k$^2$. The theory provided a good initial framework to classify structures. But as high-resolution imaging techniques progressed (cryo-EM and X-ray) more icosahedral capsids were revealed to either not comply with the theory or create doubts on how to interpret the T-number. More recently, a generalized version of this theory was introduced in Twarock and Luque 2019 . The quasiequivalence principle was applied in this case to the vertices formed by the network of proteins. The original Caspar and Klug theory relied on protein coordinated on an hexagonal lattice. The new theory showed that icosahedral capsids could be generated instead from any of the eight Archimedean lattices containing an hexagonal sublattice. The geometric organization of tailes in these lattices openede the possibilities to accommodate viruses that cluster their proteins in different local structures as well as account for viruses that contain major and minor capsid proteins.
Following up on this work, here we are exploring a computational pipeline that is able to assign the most adequate icosahedral model to a molecular capsid. The key premise is that the clusters formed by the capsid proteins must be consistent with the geometrical tiles in the icosahedral architecture.
There are other theories used to identify the positions of atoms in icosahedral capsids (Keef and Twarock 2009;Wilson 2020). Incorporating these tools to refine the characterization of the capsid anatomy would be an important next step. Additionally, it is unclear it is also possible that depending on the level of rigidity of the proteins, it would be more convenient to treat the capsid blocks based on quasirigid domains instead of chemically distinctive clusters (Polles et al. 2013). These aspects that should be investigated as a follow are discussed currently in the Impact page. Hopefully, in the near future updates of this online documentation can reflect our progress adding these features to the capsid anatomy standard.
Ackermann, Hans-W., and David Prangishvili. “Prokaryote viruses studied by electron microscopy.” Archives of Virology, 157(10): 1843-1849 (2012). https://doi.org/10.1007/s00705-012-1383-y.
Brum, Jennifer R., Ryan O. Schenck, and Matthew B. Sullivan. “Global morphological analysis of marine viruses shows minimal regional variation and dominance of non-tailed viruses.” The ISME Journal, 7(9): 1738-1751 (2013). https://doi.org/10.1038/ismej.2013.67.
Caspar, Donald LD, and Aaron Klug. “Physical principles in the construction of regular viruses.” Cold Spring Harbor Symposia on Quantitative Biology. Vol. 27. Cold Spring Harbor Laboratory Press, 1962. https://doi.org/10.1101/sqb.1962.027.001.005.
Keef, Thomas, and Reidun Twarock. “Affine extensions of the icosahedral group with applications to the three-dimensional organisation of simple viruses.” Journal of Mathematical Biology, 59(3):287-313 (2009). https://doi.org/10.1007/s00285-008-0228-5.
Krupovic, Mart, and Eugene V. Koonin. “Multiple origins of viral capsid proteins from cellular ancestors.” Proceedings of the National Academy of Sciences, 114(12): E2401-E2410 (2017). https://doi.org/10.1073/pnas.1621061114.
Montiel-Garcia, Daniel, Nelly Santoyo-Rivera, Phuong Ho, Mauricio Carrillo-Tripp, Charles L. Brooks Iii, John E. Johnson, and Vijay S. Reddy. “VIPERdb v3. 0: a structure-based data analytics platform for viral capsids.” Nucleic Acids Research, 49(D1): D809-D816 (2021). https://doi.org/10.1093/nar/gkaa1096.
Polles, Guido, Giuliana Indelicato, Raffaello Potestio, Paolo Cermelli, Reidun Twarock, and Cristian Micheletti. “Mechanical and assembly units of viral capsids identified via quasi-rigid domain decomposition.” PLoS Computational Biology 9(11):e1003331 (2013). https://doi.org/10.1371/journal.pcbi.1003331.
Twarock, Reidun, and Antoni Luque. “Structural puzzles in virology solved with an overarching icosahedral design principle.” Nature Communications, 10(1): 1-9 (2019). https://doi.org/10.1038/s41467-019-12367-3.
Wilson, David P. “Unveiling the Hidden Rules of Spherical Viruses Using Point Arrays.” Viruses, 12(4):467 (2020). https://doi.org/10.3390/v12040467.