Biophysical Society Thematic Meeting - November 16-20, 2015

Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Speaker Abstracts

Structural Biology of Some Virus Pathogens David Stuart 1,2,3 . 1 University of Oxford, Headington, United Kingdom, 2 Diamond Light Source, Oxfordshire, United Kingdom, 3 Instruct, Oxford, United Kingdom. My group study a number of viruses, some of which present significant threats to human and animal health. Most of our basic research is aimed at understanding aspects of the virus lifecycle and host interactions. However the biological mechanisms uncovered sometimes present therapeutic opportunities, which range from small molecule antivirals, through therapeutic proteins (eg antibodies) to improved vaccines. At present picornaviruses are major targets of our work: small icosahedral viruses that include an increasing number of genera and increasing structural and mechanistic diversity. I will present some snapshots of different picornaviruses to highlight how evolution can mix and match biological mechanisms in the context of a broadly conserved structural framework for the mature capsid. Whilst there are some effective vaccines against picornaviruses, which often elicit strong antibody responses against intact viruses, these are based on 50 year old technology and are usually produced in high level containment. In contrast there are no currently licensed anti-virals for any picornavirus. I will present case studies of how structural understanding seems to be helping towards both structure-guided novel antivirals, against HFMDVs (EV71 and CVA16)¬ – major public health threats in East Asia and the structure-guided design of improved vaccines, in particular (i) FMDV, where despite a vaccine the virus remains a massive problem for farming globally and in particular in South Africa and (ii) poliovirus, where whilst the disease may be almost eliminated due to a massive sustained operation by WHO the virus lives on across the globe. I hope also to consider the question of how neutralizing antibodies work, and again pose the question – can this understanding be useful? – perhaps by allowing us to aim for vaccines that give greater cross protection.

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