To elucidate the antiviral mechanism of AB138 in cells, we performed quantitative proteomic analysis on HCT-8 cells under three conditions: AB138 treatment alone, pre-treatment with 1 μM AB138 for 8 h prior to BCoV infection, and treatment with 1 μM AB138 initiated 24 h after BCoV infection. Consistent with host-target engagement, volcano plot analyses revealed extensive yet selective remodeling of the proteome in response to AB138 treatment across dosing strategies (Fig. 4G). In cells treated with AB138 alone, GSPT1 was the most substantially reduced protein, although IKZF1/3 were not detected. Following post-infection administration of AB138, significant decreases were observed in GSPT1, pro-inflammatory factors (e.g., NFKBIA, IL17RA), and apoptosis-regulating proteins (e.g., BAD, BCL2L2), whereas the interferon-associated protein IFRD1 was upregulated. In contrast, in cells pretreated with AB138 prior to BCoV infection, substantial reductions were observed in GSPT1 as well as immune-related proteins (e.g., NFKBIA, IL6ST). Conversely, levels of BAD and IFRD1 were markedly increased. These results indicate that AB138 exerts its antiviral effects, at least in part, through modulation of host inflammatory and apoptotic pathways in cells.