Targeting though viruses in the lung

Novel targets and drugs for the treatment of viral infections of the human pulmonary system

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.

Novel drugs that efficiently and safely clear viruses from the lung will decrease suffering in infants, children, and adults and lessen the burden of these viral diseases on health care resources and society in general.

Building on preliminary work, LUMC and Janssen ID&V would like to discover and validate more host-directed targets. Parallel to this discovery and validation effort, the mechanism of action and antiviral activity of certain JNJ (Johnson & Johnson) compound classes will be further evaluated. Finally, a novel in vitro model system (lamb bronchial epithelial cells) will be optimised.

Summary
In the twenty-first century, viruses infecting the human lung remain a cause of suffering in infants, children, and adults. The aim of this project is to find novel ways to help ‘ciliated lung cells’ - cells with a crown of tiny ‘hairs’ - get rid of viruses.
Technology Readiness Level (TRL)
1 - 3
Time period
24 months
Partners
Logo
Logo