The Aqueous Leaf Extract of M. oleifera Inhibits PEDV Replication through Suppressing Oxidative Stress-Mediated Apoptosis

SIMPLE SUMMARY: The porcine epidemic diarrhea virus (PEDV), a porcine enteropathogenic coronavirus, can cause enormous economic losses in the swine industry. There is no effective commercial vaccine against PEDV infection. In this study, we found that an aqueous leaf extract of M. oleifera (MOE) exhibited antiviral activity in response to PEDV infection at the stage of PEDV replication instead of attachment or internalization. Mechanistically, MOE suppressed the oxidative stress and the expression of inflammatory cytokines induced by PEDV infection and upregulated the expression of anti-apoptotic proteins, which further led to less cell apoptosis. This study is the first report showing that MOE has antiviral potential as a new prophylactic and therapeutic strategy against PEDV infection. ABSTRACT: Porcine epidemic diarrhea (PED), one of the serious enteric diseases caused by the porcine epidemic diarrhea virus (PEDV), is responsible for enormous economic losses in the global swine industry. However, available commercial vaccines fail to protect pigs from PEDV infection due to the appearance of PEDV variants. Hence, it is necessary to find an effective and cost-efficient natural product to protect pigs from PEDV infection. In this study, we first found that an aqueous leaf extract of M. oleifera (MOE) exhibited antiviral activity in response to PEDV infection. Furthermore, time-of-addition experiments revealed that MOE inhibited PEDV replication rather than attachment and internalization. Mechanistically, MOE significantly suppressed the production of reactive oxygen species (ROS) and malondialdehyde (MDA) induced by PEDV infection, and restored glutathione peroxidase (GSH-Px) activity. Importantly, the addition of MOE alleviated oxidative stress and the expression of inflammatory cytokines and resulted in fewer apoptotic cells during PEDV infection. These results indicated that MOE might be an effective anti-PEDV drug used to control PED disease and may be helpful in developing a new prophylactic and therapeutic strategy against PEDV.