Preclinical Antiviral and Safety Profiling of the HBV RNA Destabilizer AB-161.

HBV RNA destabilizers are a class of small-molecule compounds that target the noncanonical poly(A) RNA polymerases PAPD5 and PAPD7, resulting in HBV RNA degradation and the suppression of viral proteins including the hepatitis B surface antigen (HBsAg). AB-161 is a next-generation HBV RNA destabilizer with potent antiviral activity, inhibiting HBsAg expressed from cccDNA and integrated HBV DNA in HBV cell-based models. AB-161 exhibits broad HBV genotype coverage, maintains activity against variants resistant to nucleoside analogs, and shows additive effects on HBV replication when combined with other classes of HBV inhibitors. In AAV-HBV-transduced mice, the dose-dependent reduction of HBsAg correlated with concentrations of AB-161 in the liver reaching above its effective concentration mediating 90% inhibition (EC90), compared to concentrations in plasma which were substantially below its EC90, indicating that high liver exposure drives antiviral activities. In preclinical 13-week safety studies, minor non-adverse delays in sensory nerve conductance velocity were noted in the high-dose groups in rats and dogs. However, all nerve conduction metrics remained within physiologically normal ranges, with no neurobehavioral or histopathological findings. Despite the improved neurotoxicity profile, microscopic findings associated with male reproductive toxicity were detected in dogs, which subsequently led to the discontinuation of AB-161's clinical development.

Optimization of physical and dielectric properties of Co-doped ZnO nanoparticles for low-frequency devices.

In this study, zinc-oxide (ZnO) nanoparticles (NPs) doped with cobalt (Co) were synthesized using a simple coprecipitation technique. The concentration of Co was varied to investigate its effect on the structural, morphological, optical, and dielectric properties of the NPs. X-ray diffraction (XRD) analysis confirmed the hexagonal wurtzite structure of both undoped and Co-doped ZnO-NPs. Scanning electron microscopy (SEM) was used to examine the morphology of the synthesized NPs, while energy-dispersive X-ray spectroscopy (EDX) was used to verify their purity. The band gap of the NPs was evaluated using UV-visible spectroscopy, which revealed a decrease in the energy gap as the concentration of Co2+ increased in the ZnO matrix. The dielectric constants and AC conductivity of the NPs were measured using an LCR meter. The dielectric constant of the Co-doped ZnO-NPs continuously increased from 4.0 × 10-9 to 2.25 × 10-8, while the dielectric loss decreased from 4.0 × 10-8 to 1.7 × 10-7 as the Co content increased from 0.01 to 0.07%. The a.c. conductivity also increased with increasing applied frequency. The findings suggest that the synthesized Co-doped ZnO-NPs possess enhanced dielectric properties and reduced energy gap, making them promising candidates for low-frequency devices such as UV photodetectors, optoelectronics, and spintronics applications. The use of a cost-effective and scalable synthesis method, coupled with detailed material characterization, makes this work significant in the field of nanomaterials and device engineering.