Small molecule inhibitors for bovine respiratory syncytial virus
Lead Research Organisation:
University of Warwick
Department Name: School of Life Sciences
Abstract
Infection of cattle with bovine respiratory syncytial virus is a worldwide problem and results in losses of more than £150 million for the UK farming industry alone. We have shown that BRSV and related viruses express an essential protein, M2-2, by using a novel mechanism that relies on the action of a protein, DDX3 that is present in the cells that the viruses infect. If the virus M2-2 protein is not made in sufficient amounts the virus cannot grow effectively. We have identified a number of inhibitors that interfere with the action of the DDX3 protein and as a result prevent production of the M2-2 protein. This treatment prevents the growth of BRSV and its related viruses. We intend to develop these inhibitors as potential drugs to combat the virus.
Organisations
| Description | We have generated a range of potential inhibitors for respiratory syncytial virus. These have been tested in vitro and the four compounds with the best inhibition profile have been tested for their interaction with liver microsopmes to assess feature for potenmtial use in vivo. Two compounds have been tested in mice for tolerance and have been shown to be tolerated without adverse effects at the highest concentrations achievable for oral administration. |
| Exploitation Route | We have shown that these compounds are tolerated extremely well in vivo. One compound in particular showed reduction in virus yield at the levels used in animals. Work is required on some pharacokinetic studies but the data to date shows that this is a potentially promising avenue of reserch in the area of antiviral delevelopment. We have approached potential commercial collaborators to seek further inpurt and potentially funding to take this forward. |
| Sectors | Agriculture, Food and Drink,Pharmaceuticals and Medical Biotechnology |
| Title | Use of DDX3X inhibitors for the treatment of pneumovirus infections |
| Description | The work describes the discovery of small molecule inhibitors of the cellular helicase enzyme DDX3X which is essential for efficient replication of human respiratory syncytial virus. The discovery has extended the scope of using small molecule inhibitors to reduce the efficiency of pneumovirus replication in vitro and in vivo. T |
| IP Reference | |
| Protection | Patent application published |
| Year Protection Granted | 2015 |
| Licensed | No |
| Impact | The discovery has extended the scope of using small molecule inhibitors to reduce the efficiency of pneumovirus replication in vitro and in vivo. The discovery and description of a broad range of related molecules provides the opportunity to generate effective small molecule inhibitors to prevent pneumovirus-associated disease in humans and animals. |