Sofosbuvir (1)

Yoosefian M, et al. Journal of Molecular Liquids, 2025, 426, 127304.

This study investigated the antiviral efficacy of Sofosbuvir and its structural analogs through in silico methods targeting the HCV NS5B polymerase. Gaussian-based quantum chemical calculations and molecular docking were employed to evaluate electronic properties and binding affinities. Among the analogs, SOFO5 demonstrated significantly stronger binding energy to the NS5B active site than Sofosbuvir, suggesting superior inhibitory potential. Subsequent molecular dynamics simulations validated the stability and interaction persistence of the SOFO5-NS5B complex over time, supporting its structural compatibility and therapeutic promise. These findings underline SOFO5 as a potent NS5B_P inhibitor and a promising lead candidate for further preclinical development in HCV therapy. The experimental framework integrating docking and dynamic simulations effectively elucidated the interaction profile and pharmacological advantage of SOFO5 over the parent compound, Sofosbuvir.

Jagst M, et al. Antiviral Research, 2024, 227, 105922.

This study investigated the antiviral efficacy of sofosbuvir against Hepatitis E virus (HEV) in extrahepatic neuronal-derived cells. Neuronal cell lines were infected with HEV and treated with sofosbuvir or NITD008, both known viral polymerase inhibitors. Viral replication levels were quantified using RT-qPCR to assess intracellular HEV RNA, while immunofluorescence assays confirmed viral protein expression. Compared to hepatoma cells, sofosbuvir demonstrated a significantly reduced antiviral effect in neuronal cells, indicating cell-type-dependent differences in drug responsiveness. Despite diminished efficacy, sofosbuvir was able to inhibit HEV replication to a measurable extent in neuronal models, highlighting its potential for addressing HEV-related neurological manifestations. These findings underscore the importance of evaluating direct-acting antivirals like sofosbuvir across diverse cell types, particularly those representing extrahepatic viral reservoirs.