Identification and in vivo Efficacy Assessment of Approved Orally Bioavailable Human Host Protein-Targeting Drugs With Broad Anti-influenza A Activity
Theresa Enkirch, Svenja Sauber, Danielle E Anderson, Esther S Gan, Dimitar Kenanov, Sebastian Maurer-Stroh, Veronika von Messling
Frontiers in Immunology | FRONTIERS MEDIA SA | Published : 2019
The high genetic variability of influenza A viruses poses a continual challenge to seasonal and pandemic vaccine development, leaving antiviral drugs as the first line of defense against antigenically different strains or new subtypes. As resistance against drugs targeting viral proteins emerges rapidly, we assessed the antiviral activity of already approved drugs that target cellular proteins involved in the viral life cycle and were orally bioavailable. Out of 15 candidate compounds, four were able to inhibit infection by 10- to 100-fold without causing toxicity, in vitro. Two of the drugs, dextromethorphan and ketotifen, displayed a 50% effective dose between 5 and 50 μM, not only for the..View full abstract
Awarded by A*STAR grant
This work was supported in part by funding from the German Center for Infection Research, the German Ministry of Health, and a DUKE-NUS Signature Research Program start-up grant funded by the Agency for Science, Technology, and Research (A*STAR), Singapore and the Ministry of Health, Singapore to VvM, and A*STAR grant H1699f0013 to SM-S.