Zika Antiviral Therapy Candidate Identified

A Dutch biopharmaceutical company announced the publication of promising preclinical in-vivo trial results, showing the efficacy of its Aryl Hydrocarbon Receptor (AHR) inhibitor HP163 against Zika virus infection and potentially against Corona-virus infection.

AHR inhibition with HP163 blocked Zika virus replication and ameliorated newborn microcephaly in a murine model.

Hercules Pharmaceuticals said on August 20, 2020, in Nature Neuroscience that Hercules' AHR inhibitor HP163 reduces viral replication in animals infected with Zika-virus and reduced microencephaly. This study identified AHR as a host factor for ZIKV replication and promyelocytic leukemia (PML) protein as a driver of anti-ZIKV intrinsic immunity.

In addition, a pre-publication of an article on Research Square concludes that AHR inhibition may also be effective against coronavirus infections via a similar mechanism. AHR antagonists decrease viral titers and ameliorate ZIKV-induced pathology in vivo. 

This report found that AHR is activated during coronavirus infection, impacting anti-viral immunity, and lung basal cells associated with tissue repair.

Hence, AHR antagonists are candidate therapeutics for the management of coronavirus-infected patients.

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 anti-viral immunity driven by PML protein, resulting in increased viral replication.

The successful development of AHR inhibitors could lead to the 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. A remedy is urgently needed to treat Zika and dengue infection.”

Hercules Pharmaceuticals is a Dutch private biopharmaceutical company, focusing on developing small molecule inhibitors of the Aryl Hydrocarbon Receptor for the treatment of cancer and viral infections.

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