Abstract
During the development of single particle cryo-EM in past five decades, icosahedral viruses have led the resolution progress owing to their large mass and high symmetry. Many technical advances in cryo-EM were first established with viruses. Since reaching ∼4Å resolution in 2008, it has become a relatively routine task to solve the atomic structure of isolated viruses. The future of structural virology will be increasingly focused on remaining challenges including solving structures of jumbo viruses, intermediate functional states during assembly, maturation, and infection, and in situ structures. Recent demonstrations of near-atomic resolution structure with electron tomography and sub-tomogram averaging opens a new direction for high resolution studies of pleomorphic viruses and the pleomorphic states of icosahedral viruses that have defied past efforts using the single particle cryo-EM approach.