Scientific Reports - Screening great ape museum specimens for DNA viruses

In chronic HBV carrier mice, SHARP vaccine variants showed promise toward durable viral control.

This study investigates the presence and genetic characteristics of hepatitis B virus (HBV) in non-human primates (NHPs) and their human caretakers across four major Indonesian islands. Researchers screened 237 NHPs from 10 species alongside 65 human caretakers, identifying HBV DNA in East Javan langurs, gibbons, orangutans, and humans. Serological evidence of exposure was found in multiple species, with notable prevalence in gibbons and orangutans. Phylogenetic analysis placed langur HBV strains within the gibbon clade, raising questions about cross-species transmission mechanisms due to genetic differences between langurs and gibbons. The study highlights the potential for zoonotic spread and underscores the need for continued surveillance at primate-human interfaces. Findings suggest widespread HBV circulation among Old World monkeys, with immune responses like HBsAb indicating prior exposure. These results contribute to understanding HBV's ecological dynamics and public health implications in regions where human-primate interactions are common.

Targeting the capsid protein of the hepatitis B virus (HBV) has emerged as a promising strategy for developing new antiviral therapies. In this study, we report the discovery of a novel series of pyrrole oxo-carboxamide compounds as HBV capsid assembly modulators (CAMs) that block viral replication. Through a process of focused structure–activity relationship (SAR) optimization, we identified compound 12 (VNRX-9945), which exhibited excellent and broad antiviral activity against multiple HBV genotypes in vitro, along with favorable pharmacokinetic profiles across multiple species. Additionally, 12 demonstrated robust efficacy in the adeno-associated virus mouse model of HBV (AAV-HBV) infection. This compound has advanced into Phase 1 clinical trials to evaluate its safety and pharmacokinetics in healthy volunteers, to enable treatment of chronic HBV infections.

In two duplicate phase 3 trials, bepirovirsen led to a functional cure among patients with chronic HBV infection after discontinuing nucleoside or nucleotide analogue therapy.