2026-10-13T10:22:52Z https://www.scidb.cn/oai

10.57760/sciencedb.38539 2026-07-28T14:38:23Z

2026-07-28 Coptisine-naringenin combination inhibits PRRSV replication via the MET/PI3K/Akt pathway thereby attenuating virus-induced mitochondrial apoptosis doi:10.57760/sciencedb.38539 en Porcine reproductive and respiratory syndrome virus (PRRSV) remains a major threat to the global swine industry due to its high genetic diversity and cross-genotype infectivity, with limited effective control measures available. In our previous work, six natural compounds-ferulic acid, kaempferol, choline, coptisine, quercetin, and naringenin-were identified to inhibit PRRSV replication in Marc-145 and PAM cells. In this study, we performed a systematic combination optimization of these six compounds to develop a synergistic anti-PRRSV formulation. First, network pharmacology was employed to predict the potential targets of the six compounds against PRRSV, and differential target profiles guided the initial design of compound combinations. Subsequently, a six-factor, three-level orthogonal design was applied to construct multi-compound formulations, and the Chou-Talalay method was used to evaluate two-compound combinations. The safety of each formulation was assessed in Marc-145 cells by CCK-8 assay, and the anti-PRRSV efficacy was determined by RT-qPCR and Western blot analysis of PRRSV N gene and protein expression. Through this stepwise screening, the optimal synergistic pair was identified as coptisine and naringenin at a molar ratio of 50 μM : 36.73 μM. This combination significantly suppressed PRRSV replication in vitro. Using network pharmacology and molecular docking, we further revealed that the coptisine-naringenin formulation targets host MET protein, inhibits PRRSV-induced activation of the PI3K/Akt signaling pathway, thereby reducing viral load and consequently suppressing the mitochondrial apoptosis pathway triggered by PRRSV. Collectively, our findings highlight a novel, rationally designed synergistic formulation of Coptisine and Naringenin that counteracts PRRSV through host MET/PI3K/Akt axis, offering a promising lead for antiviral drug development. PRRSV; Compound formulation; Coptisine; Naringenin; PI3K/Akt signaling pathway; Apoptosis Yizhen Jia PUBLIC https://creativecommons.org/licenses/by/4.0/ dataset Science Data Bank