Matriptase belongs to the family of type 2 serine proteases and is widely expressed on epithelial tissues, including the lung. Recent studies have demonstrated the ability of matriptase to proteolytically activate th hemagglutinin precursor HA0 into HA1, an obligatory step performed by enzymes of the host in order to initiate the replication of the influenza virus. This obligatory step presents an opportunity for the development of new treatments targeting the host and not the highly mutable virus, with the goal to provide an approach which will escape the high levels of resistance encountered by current anti-influenza treatments.We report herein new peptidomimetic inhibitors of matriptase in the form of slow, tight-binding inhibitors. The design, synthesis, selectivity and activity of this new class of inhibitors against the influenza H1N1 virus in vitro will be presented, as well as a molecular model of the inhibitor docked into the enzyme active site.

New matriptase inhibitors as a potential treatment against influenza

245th National Meeting (2013)

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