Imatinib Mesylate as an Effective Anti-viral Treatment for Alphavirus Infections

Abstract

Alphaviruses are plus-strand RNA viruses that are transmitted by mosquitoes. There are very limited vaccines and treatment options available to those infected with alphaviruses, resulting in significant human and animal morbidity and mortality each year. Viruses are parasites of host cell metabolism and alphaviruses have been shown to increase glycolytic flux during infection to aid viral replication. Imatinib mesylate is an FDA-approved tyrosine kinase inhibitor that is used to treat several types of cancers. A hallmark of tumorous cells is an elevated metabolic rate and Imatinib successfully slows metabolism by inhibiting tyrosine kinases that are required to activate metabolic enzymes, such as hexokinase in the glycolytic pathway. It was hypothesized that Imatinib could be used to slow metabolism in virally-infected cells and reduce viral replication. Alphavirus-infected cells were treated with various concentrations of Imatinib and at a concentration of 6 µM, viral replication was reduced by more than 40% while cell viability was still at 100%. The efficacy of Imatinib treatment at inhibiting alphavirus replication was confirmed at different times post infection (6, 12, 18, and 24 hours post infection), different levels of infection (multiplicities of infection= 0.1, 1, and 10), and within different cell lines (BHK, Huh7 and HEK). Further analysis in mouse or other animal models is needed to confirm the utility of Imatinib as a therapeutic option for treating alphavirus infection, but the data are promising and shows a significant reduction in viral replication and may represent a novel treatment option for alphavirus infections.