Ivermectin Inhibits the Replication of Usutu Virus In Vitro

Usutu virus (USUV) is an emerging mosquito-borne arbovirus within the genus Flavivirus, family Flaviviridae. Similar to the closely related West Nile virus (WNV), USUV infections are capable of causing mass mortality in wild and captive birds, especially blackbirds. In the last few years, a massive spread of USUV was present in the avian population of Germany and other European countries. To date, no specific antiviral therapies are available. Nine different approved drugs were tested for their antiviral effects on the replication of USUV in vitro in a screening assay. Ivermectin was identified as a potent inhibitor of USUV replication in three cell types from different species, such as simian Vero CCL-81, human A549 and avian TME R. A 2- to 7-log10 reduction of the viral titer in the supernatant was detected at a non-cytotoxic concentration of 5 µM ivermectin dependent on the applied cell line. IC(50) values of ivermectin against USUV lineage Africa 3 was found to be 0.55 µM in Vero CCL-81, 1.94 µM in A549 and 1.38 µM in TME-R cells. The antiviral efficacy was comparable between the USUV lineages Africa 2, Africa 3 and Europe 3. These findings show that ivermectin may be a candidate for further experimental and clinical studies addressing the treatment of USUV disease, especially in captive birds.