Biophysical Society Thematic Meeting

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

Structural Biology of Some Virus Pathogens

David Stuart

1,2,3

University of Oxford, Headington, United Kingdom,

Diamond Light Source, Oxfordshire,

United Kingdom,

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.