Reducing viral replication by aryl hydrocarbon receptor inhibition

Hercules Pharmaceuticals has announced the publication of promising preclinical in vivo trial results showing efficacy of its aryl hydrocarbon receptor (AhR) inhibitor HP163 against Zika virus infection and potentially against coronavirus.

A recent publication in Nature Neuroscience reported that Hercules’ AhR inhibitor HP163 reduces viral replication in animals infected with Zika virus (pictured) and reduced microencephaly. In vitro studies also showed efficacy of AhR inhibitors against dengue, a related virus.

In addition, a pre-publication of an article on Research Square concludes that AhR inhibition may also be effective against SARS-CoV-2 and other coronavirus infections via a similar mechanism.

It was found that virus infection triggers AhR activation, limiting the production of type I interferons (IFN-I) involved in antiviral immunity. Moreover, AhR activation suppressed intrinsic antiviral immunity driven by the promyelocytic leukaemia (PML) protein, resulting in increased viral replication. AhR inhibition with Hercules’ HP163 blocked Zika virus replication and ameliorated newborn microcephaly in a murine model.

Successful development of AhR inhibitors could lead to oral treatment of patients with early stages of virus infection.