Ginsenoside Rb1 inhibits porcine epidemic diarrhea virus replication through suppressing S1 protein mediated the MAPK/ERK pathway and reducing apoptosis.

Porcine epidemic diarrhea virus (PEDV) causes vomiting, dehydration, and diarrhea in piglets, seriously threatening their survival and development and causing huge economic losses to the global pig industry. Current PEDV control relies on vaccines, however, the high mutation rate of PEDV limits vaccine effectiveness, highlighting the need for new antiviral drugs. This study investigated the pharmacological effects of ginsenoside Rb1 (GRb1) on PEDV using network pharmacology, as well as GO and KEGG analyses, to predict its role in modulating the MAPK/ERK pathway. GRb1 downregulated the MAPK/ERK pathway activated by PEDV infection and reduced levels of the apoptotic protein cleaved-caspase-3, thus inhibiting PEDV-induced apoptosis and demonstrating antiviral properties. Further screening showed that the PEDV S1 protein promotes AP-1 nuclear entry and upregulates the MAPK/ERK pathway to induce apoptosis, a process reversed by GRb1. Further in vivo studies revealed that GRb1 treatment significantly reduced viral load in piglet intestinal tissues and anal swabs. GRb1 also alleviated clinical symptoms and intestinal damage in infected piglets, improving their survival rate while also downregulating the levels of inflammatory factors (IL-1β, IL-6, IL-8, and TNF-α). This study is the first to demonstrate that GRb1 effectively inhibits PEDV, uncovering its potential mechanism of action and providing a promising new approach for antiviral treatment in veterinary medicine.