Atriva scientists were invited to give an overview talk on their antiviral MEK inhibitor concept at the 30th International Conference of Antiviral Research (ICAR2017) that was held from May 21-25, 2017, in Atlanta/Georgia.
The annual ICAR is the most important conference series in the antiviral research field and gathers experts from academia and the industry.
The talk was entitled "Repurposing Kinase Inhibitors Against Influenza – The Clinically Approved MEK Inhibitor Trametinib Efficiently Blocks IAV Propagation and Limits Hyperexpression of Cytokines" and was presented on May 24th, 2017 in the "Respiratory Virus" session.
Repurposing Kinase Inhibitors Against Influenza – The Clinically Approved MEK Inhibitor Trametinib Efficiently Blocks IAV Propagation and Limits Hyperexpression of Cytokines
Tobias Schräder, PhD1, Sabine Dudek, PhD1, Christina Ehrhardt, MD, PhD1, Oliver Planz, PhD2, Stephan Ludwig, PhD1
1 Institute of Virology (IVM) Westfaelische Wilhelms-University Muenster, Muenster, Germany;
2 Interfaculty Institute for Cell Biology, University of Tuebingen, Germany, Tuebingen
Influenza A virus (IAV) infections are still a major global threat for humans. The currently licensed anti-viral drugs target viral factors and are prone to provoke viral resistance. Thus there is an urgent need for effective antivirals to fight IAV. In infected host cells IAV induces various cellular signaling cascades. We have shown previously that the Raf/MEK/ERK signaling cascade is indispensable for IAV replication because it triggers the nuclear export of newly assembled viral ribonucleoproteins (vRNPs). Inhibition of this cascade limits viral replication. Thus, next to their potential in anti-tumor therapy, inhibitors targeting the Raf/MEK/ERK signaling cascade came into focus as potential anti-viral drugs. The first licensed MEK inhibitor Trametinib (GSK-1120212) is used for treatment of malignant melanoma, being highly selective and having a very promising side effect profile. Since Trametinib may be qualified for a repurposing approach that would significantly shorten development time for an anti-flu use, we evaluated its anti-viral potency and mode of action. In this study, we describe that Trametinib efficiently blocks replication of different influenza subtypes in vitro and in vivo. The broad anti-viral activity against various IAV strains was due to its ability to interfere with export of progeny vRNPs from the nucleus. The compound also limited hyper-expression of several cytokines. Thus, we show for the first time that a clinically approved MEK inhibitor acts as a potent antiinfluenza agent.
Prof. Stephan Ludwig did the presentation.