Abstract
Outbreaks and the widespread prevalence of porcine respiratory infectious diseases have led to substantial economic losses worldwide. In this study, epidemiological surveillance revealed lower viral detection in association with an increased abundance of Bacillaceae in pigs with outdoor access; thus, Bacillus subtilis NS12, a strain with enhanced mucosal colonization and superior broad-spectrum antiviral activity, was isolated from the nasal mucosa of these pigs for further investigation. This mechanistic study revealed that the antiviral efficacy of B. subtilis NS12 is primarily attributed to bioactive metabolites, including a novel surfactin with high safety and antiviral activity and piceatannol, a potent antioxidant molecule. These metabolites modify the structure and fluidity of phospholipids within the viral envelope, thereby inhibiting viral entry by impeding membrane fusion. Therefore, with its broad-spectrum antiviral activity, B. subtilis NS12 offers a probiotic-based, environmentally sustainable, and noninvasive antiviral strategy for preventing and controlling respiratory viral infections.