FDA-drug screening identifies deptropine inhibiting hepatitis E virus involving the NF- κB-RIPK1-caspase axis.

In this study, we performed a screening of a library containing over 1,000 FDA-approved drugs. We have identified deptropine, a classical histamine H1 receptor antagonist used to treat asthmatic symptoms, as a potent inhibitor of HEV replication. The anti-HEV activity of deptropine appears dispensable of the histamine pathway, but requires the inhibition on nuclear factor-κB (NF-κB) activity. This further activates caspase mediated by receptor-interacting protein kinase 1 (RIPK1) to restrict HEV replication. Given deptropine being widely used in the clinic, our results warrant further evaluation of its anti-HEV efficacy in future clinical studies. Importantly, the discovery that NF-κB-RIPK1-caspase pathway interferes with HEV infection reveals new insight of HEV-host interactions.
PMID: 31415805 [PubMed - as supplied by publisher]

Source: Antiviral Research - August 11, 2019 Category: Virology Authors: Qu C, Li Y, Li Y, Yu P, Li P, Donkers JM, van de Graaf SF, de Man RA, Peppelenbosch MP, Pan Q Tags: Antiviral Res Source Type: research