New thiourea derivatives that target the episomal silencing SMC5 protein to inhibit HBx-dependent viral DNA replication and gene transcription.

ABSTRACT: Antivirals such as nucleotide analogs (NAs) are potent inhibitors of hepatitis B virus (HBV) replication. However, NAs fail to diminish the signaling and mitogenic activities of the transactivator HBx protein. Earlier we have shown that thiourea derivative IR-415 (DSA-00) targeted HBx to down-regulate its target viral and host genes. However, the molecular mechanism of its antiviral action is poorly understood. Here we investigated the anti-HBV properties of DSA-00 and its new derivatives in cell culture models. DSA-00 and its derivatives DSA-02 and DSA-09 not only suppressed HBV DNA levels similar to well-known antiviral Entecavir but also diminished the expression of pgRNA and secretion of HBsAg and HBeAg. Apparently, the three DSA derivatives inhibited the viral pregenomic RNA expressio

SUBMITTER: Kumar J 

PROVIDER: S-EPMC11635082 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature