Targeting though viruses in the lung
Respiratory viral infections are a major cause of morbidity and mortality in infants, children, and adults. The social and economic impact of respiratory viral diseases varies from serious (RSV, Influenza virus) to crippling (Coronaviridae). The cost of human lives is unacceptably high which is demonstrated by the recent COVID-19 crisis, but it should be clear that these infections have always been an under appreciated cause of human suffering and death in The Netherlands, Europe, and the world.
The epithelial cells lining the bronchial tree (airways of the lung) represent the first line of defense against microbial invaders but are also the primary targets of respiratory viruses. This holds especially true for ciliated cells which carry a crown of ‘hair-like protrusions’ and clear mucus with unwelcome microbial invaders from the lung. Unfortunately, viruses such as RSV, Coronaviridae and Influenza virus strains infect these ciliated cells. Direct antiviral compounds may be unable to completely clear the virus from the lung in a timely fashion. Therefore, LUMC and Janssen Infectious Diseases & Vaccines (Janssen ID&V) would like to discover host-directed targets in ciliated cells to complement direct antiviral therapy. Host-directed targets are components (such as proteins) in the cell that are exploited by the virus for generating multiple copies of itself.
During this research collaboration, the existence of (potentially druggable) host-directed targets was demonstrated. This will aid in our scientific understanding of the mechanisms of viral entry and replication in the host cell (scientific impact). Furthermore, as these targets are potentially druggable, direct antiviral therapy could be significantly supplemented with drugs that act upon host-directed targets. This is a significant finding considering the unmet need in respiratory viral infections caused by RSV or respiratory viruses with pandemic potential. With respect to economic impact, the discovery of host-directed targets enables Janssen to access immediately the therapeutic potential of these findings.
