Antiviral activity of the non-steroidal anti-inflammatory drug indomethacin against Respiratory Syncytial Virus

Human respiratory syncytial virus (RSV) is a ubiquitous pathogen belonging to thePneumoviridaefamily. The enveloped virion contains a single-stranded, negative-sense RNA genome comprising 10 genes encoding 11 proteins. Infection is critically dependent on the RSV fusion (F)-protein, which mediates fusion between the viral envelope and host cells, as well as fusion of infected cells with adjacent cells, resulting in syncytium formation. RSV is the leading cause of hospitalization in children younger than 5-years of age with acute respiratory infections, posing a high risk of bronchiolitis and severe pneumonia particularly in infants under 6-months of age. RSV is also recognized to cause a substantial health burden in older adults. Virus-triggered exacerbated inflammation is associated with severe RSV disease outcomes. Although several F-targeting vaccines and monoclonal antibodies are now available for prevention of RSV disease in infants and older adults in several countries, there is no effective specific drug treatment for RSV. Herein we show that the non-steroidal anti-inflammatory drug indomethacin has a remarkable antiviral activity against RSV, causing a decrease in infectious virus production in different types of human respiratory cells at low micromolar concentrations. Whereas the mechanisms underlying the antiviral activity against RSV remain to be elucidated, we found that indomethacin does not affect RSV adsorption or entry into host cells, but acts at postentry level interfering with F-protein expression. The results suggest that indomethacin, possessing both anti-inflammatory properties and a direct antiviral activity against RSV, may represent an useful tool for the treatment of respiratory syncytial virus infections.