The article, now available in the online edition of Nature (http://dx.doi.org/10.1038/nature21032), describes the work performed at Dr Brummelkamp’s laboratory at the Netherlands Cancer Institute. The study revealed the unexpected role of a bacterial clearance pathway in the picornavirus life cycle and further demonstrated that a key enzyme used by the virus to evade clearance (PLA2G16) represents a first-in-class drug target for a broad range of picornaviruses. The picornavirus family leads to more frequent human infections than any other virus family and causes diseases such as the common cold and polio. Aided with a set of elegant haploid genetic screening experiments, first author Jacqueline Staring and co-workers unravelled a novel aspect of the molecular process responsible for how picornaviruses infect their human host cells. Inhibition of PLA2G16, a cellular and drugable enzyme, surrenders picornavirus particles to a clearance mechanism normally associated with bacterial infections. Animals in which the enzyme was inactivated were protected against infection whilst otherwise being healthy and fertile.
“These findings suggest that PLA2G16 can be exploited as novel antiviral target for diseases caused by picornaviruses. Furthermore, as such drugs would target a host factor rather than a viral protein, there would be a high barrier for the virus to develop drug resistance”, explains Dr Thijn Brummelkamp.
Haplogen holds the exclusive rights to use PLA2G16 against viral infections. In a partnership with Evotec, announced in November 2012, it has developed novel inhibitor compounds, which it anticipates to enter pre-clinical development in the course of 2017.
“We are thrilled by the extraordinary scientific achievements of our co-founder and his team”, comments Dr Georg Casari, Chief Executive Officer of Haplogen. “It is fascinating that our target PLA2G16 is linked to a new step in the life cycle of these well-studied viruses and this further validates our drug discovery programme.”
Dr Werner Lanthaler, Chief Executive Officer of Evotec, added: “We are delighted to work with Haplogen and apply our drug discovery expertise to this exciting first-in-class target. We congratulate Dr Brummelkamp and his team and look forward to continuing the relationship to develop a novel drug candidate.”
Reference: “PLA2G16 represents a switch between entry and clearance of Picornaviridae”, Jacqueline Staring, Eleonore von Castelmur, Vincent A Blomen, Lisa G. van den Hengel, Markus Brockmann, Jim Baggen, Hendrik Jan Thibaut, Joppe Nieuwenhuis, Hans Janssen, Frank van Kuppeveld, Anastassis Perrakis, Jan E. Carette & Thijn R. Brummelkamp ; Nature (2017) (http://dx.doi.org/10.1038/nature21032)
About Haplogen GmbH
Haplogen GmbH is a privately held biotechnology company in Vienna, Austria, with active programs designed to combat viral infectious diseases. For more information on Haplogen visit: www.haplogen.com.