99 / 2024-10-26 11:36:42

A Novel Approach to Combat African Swine Fever —— Disrupting Cholesterol Synthesis

African Swine Fever (ASF) is a highly contagious viral disease posing severe risks to global pig populations and food security. This study investigates the potential of cholesterol synthesis inhibitors, specifically simvastatin and AM580, to suppress ASF virus (ASFV) replication in porcine alveolar macrophages (PAM). We found that pre-treatment with these inhibitors significantly reduced ASFV replication, as demonstrated by decreased GFP-positive cell rates and total fluorescence intensity at concentrations of 5 μM, 10 μM, and 20 μM. Quantitative PCR analysis confirmed the downregulation of key ASFV protein-encoding genes B646L, MG110-3L, and X69R, with simvastatin showing superior efficacy in reducing viral titers by nearly 2 LOG levels at 5 μM. Additionally, both inhibitors significantly downregulated interferon and interferon-stimulating factor gene expressions, underscoring their impact on the host immune response. These findings highlight cholesterol synthesis inhibition as a promising therapeutic strategy against ASFV, integrating veterinary medicine and biochemistry under the "One Health" framework to enhance disease management efforts and reduce reliance on traditional culling methods.