4 pm
Thursday 14th January 2016
Physics Lecture Theatre (PLT)
Royal Society of Chemistry Seminar Series
When Biology and Chemistry Come Together: The Identification of a Novel Target for Antiviral Therapy
Prof. Andrew Easton
School of Life Sciences, University of Warwick
Human respiratory syncytial virus (HRSV) is the major cause of hospitalisation of infants with respiratory virus infection
worldwide with an estimated 160,000 deaths. HRSV also poses a serious threat to the elderly population. Currently,
there is no vaccine for HRSV and no effective therapeutic strategy. HRSV produces 10 mRNAs that encode 11 proteins
and to achieve this uses a process of coupled translation termination/reinitiation to express the regulatory M2‐2
protein from a second ORF in the M2 mRNA. We have characterised this process and have identified a highly structured
element in the mRNA that is essential for the production of M2‐2 protein. This structured region causes ribosomes to
pause which is essential for the reinitiation event that produces M2‐2 protein. We have shown that the cellular DDX3
protein binds this region of the M2 mRNA and plays a central role in coupled translation to produce the M2‐2 protein.
The requirement for DDX3 was demonstrated directly by inhibition with a small molecule inhibitor that significantly
reduced virus replication in vitro in a dose‐dependent manner opening up a new approach for antiviral treatment. In
conjunction with chemistry colleagues we have identified a class of potential new antiviral compounds.