AhR inhibitor HP163 eyes Zika...and maybe COVID-19

Hercules’ AhR inhibitor HP163 blocks viral replication in Zika infection, and potentially in COVID-19

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LEIDEN, the Netherlands—Hercules Pharmaceuticals, Inc., a Dutch biopharmaceutical company focusing on developing small molecule inhibitors of the aryl hydrocarbon receptor (AhR) for the treatment of cancer and viral infections, has announced the publication of promising preclinical in vivo trial results showing efficacy of its AhR inhibitor HP163 against Zika virus infection — and potentially against coronavirus infection.
The company has also secured new funding to test the efficacy of the compound against COVID-19, and to generate backup AhR inhibitors.
A recent publication in Nature Neuroscience reported that Hercules’ AhR inhibitor HP163 reduces viral replication in animals infected with Zika virus, and reduced microencephaly. In vitro studies also showed efficacy of AhR inhibitors against dengue. And a pre-publication of an article on Research Square has concluded that AhR inhibition could be effective against COVID-19 and other corona virus infections, via a similar mechanism.
It has been found that virus infection triggers AhR activation — which limits the production of type I interferons (IFN-I) involved in antiviral immunity. AhR activation suppressed intrinsic anti-viral immunity driven by the promyelocytic leukemia protein, which resulted in increased viral replication. HP163 blocked Zika virus replication, and ameliorated newborn microcephaly in a murine model.
The successful development of AhR inhibitors could lead to oral treatment of patients with early stages of virus infection.
“We are excited by the novel finding that the Aryl Hydrocarbon Receptor acts as a host factor for viral infections to allow viral replication,” said Bart Wuurman, CEO of Hercules Pharmaceuticals. “A remedy is urgently needed to treat zika and dengue infection, but mentioned studies also suggest that AhR inhibitors might be an effective oral treatment of patients with Covid-19, the virus which is holding our daily life hostage at this moment.”
Hercules also plans to investigate the potential of its AhR-inhibitors for treatment of COVID-19 infections. The company plans to generate additional novel AhR inhibitors for both anti-viral and cancer treatment.
To fund this program, Hercules has received an investment from Groningen-based Pharma Connect Capital and a grant from Samenwerkingsverband Noord Nederland. As part of the investment, Hercules will relocate to Groningen.

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