Remdesivir

Pentyala A, et al. Drug Metabolism and Disposition, 2025, 53(10), 100158.

This case study highlights the experimental application of remdesivir as a mechanistic probe to characterize CES2 inhibition. CES2 activity was quantified using hydrolysis assays in the presence of escalating remdesivir concentrations, revealing a nanomolar-range inhibitory effect. Time-dependent inhibition was assessed through preincubation experiments (5-40 min), demonstrating an IC₅₀ shift from 0.188 μM to 0.068 μM. Kinetic parameters were determined via kinact/KI evaluation (1.6 × 10³ M⁻¹·s⁻¹), confirming irreversible inactivation. Equilibrium dialysis and substrate-protection assays experimentally validated covalent modification of the catalytic serine. Complementary in silico docking further supported remdesivir's phosphate-mediated active-site engagement, establishing its utility as an experimental tool for probing CES2-mediated prodrug metabolism.

Lee AR, et al. Immunology Letters, 2025, 275, 107009.

This case study highlights the experimental use of Remdesivir in a collagen-induced arthritis (CIA) model to assess its immunomodulatory effects beyond antiviral activity. In DBA/1J mice, type II collagen was administered to establish CIA, followed by subcutaneous Remdesivir injections three times weekly for seven weeks. Arthritis scores and incidence were monitored biweekly. Histological assays quantified synovial inflammation and cartilage erosion. Flow cytometry evaluated IL-17⁺ CD4⁺ T-cell differentiation in splenic lymphocytes. In parallel, RA-derived fibroblast-like synoviocytes were stimulated with TNF-α and treated with Remdesivir, followed by western blot detection of STING-NF-κB signaling and necroptosis markers (RIPK3, p-MLKL). These experiments demonstrate Remdesivir's capacity to suppress STING activation, inhibit inflammatory cytokines, and attenuate joint damage.