AS-IV exhibits anti-SADS-CoV effects through the inhibition of the MAPK/JNK signaling pathway mediated by the S1 protein.

Abstract

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a porcine intestinal alpha coronavirus that infects newborn piglets. Clinical symptoms include acute diarrhea, vomiting, dehydration, and death. There is no effective prevention and control vaccine yet, so new measures are urgently needed, including antiviral strategies. Astragaloside IV (AS-IV) has several pharmacological properties, including immunomodulatory, anti-inflammatory, and antiviral effects. This research found that AS-IV inhibited SADS-CoV replication in vitro through antagonizing the MAPK/JNK pathway mediated by SADS-CoV S1 protein and reducing apoptosis. In addition, SADS-CoV S1 protein interacted with RPSA to activate MAPK/JNK pathway to facilitate virus replication. AS-IV reduced the clinical symptoms and intestinal pathological damage caused by SADS-CoV infection. AS-IV significantly reduced the viral loads in the intestinal tissue and anal swabs, and increased survival of infected piglets, suggesting that AS-IV is a potential antiviral drug for the prevention and control of SADS-CoV. Additionally, in vitro and in vivo experiments showed that AS-IV downregulated the levels of inflammatory factors, including IL-1β, IL-6, IL-8 and TNF-α, indicating that AS-IV ameliorated SADS-CoV infection-induced inflammatory response. In conclusion AS-IV exerts antiviral effects and anti-inflammatory responses through inhibiting the MAPK/JNK signaling pathway mediated by SADS-CoV S1. This study provides a theoretical basis for the research and development of anti-SADS-CoV drugs.