In Vitro Antiviral Activities of Salinomycin on Porcine Epidemic Diarrhea Virus

Abstract

Porcine epidemic diarrhea virus (PEDV), an enteropathogenic coronavirus, has catastrophic impacts on the global pig industry. Owing to the lack of effective vaccines and specific therapeutic options for PEDV, it is pertinent to develop new and available antivirals. This study identified, for the first time, a salinomycin that actively inhibited PEDV replication in Vero cells in a dose-dependent manner. Furthermore, salinomycin significantly inhibited PEDV infection by suppressing the entry and post-entry of PEDV in Vero cells. It did not directly interact with or inactivate PEDV particles, but it significantly ameliorated the activation of Erk1/2, JNK and p38MAPK signaling pathways that are associated with PEDV infection. This implied that salinomycin inhibits PEDV replication by altering MAPK pathway activation. Notably, the PEDV induced increase in reactive oxidative species (ROS) was not decreased, indicating that salinomycin suppresses PEDV replication through a pathway that is an independent pathway of viral-induced ROS. Therefore, salinomycin is a potential drug that can be used for treating PEDV infection.

Construction of a Recombinant Porcine Epidemic Diarrhea Virus Encoding Nanoluciferase for High-Throughput Screening of Natural Antiviral Products

“…The development of effective antiviral agents is another strategy to control PEDV infection. Salinomycin [ 39 ] and remdesivir [ 40 ] have been reported as potential antiviral drugs against PEDV infection in vitro. Several natural products extracted from plants, such as glycyrrhizin [ 16 ], quercetin 7-rhamnoside [ 15 ], and epigallocatechin-3-gallate [ 41 ], have been demonstrated to reduce PEDV infection in Vero cells.…”

Levistolide A Inhibits PEDV Replication via Inducing ROS Generation

“…Quercetin 7-rhamnoside mainly exerted antiviral activity during the period for attachment and entry [48]. Moreover, Salinomycin was also documented to affect PEDV penetrating Vero cells [49]. This study illustrated LA to mainly inhibit PEDV during 0-2 hpi, while this period has been defined as the main stage for the attachment and entry of PEDV [50,51].…”

Natural Compound ZINC12899676 Reduces Porcine Epidemic Diarrhea Virus Replication by Inhibiting the Viral NTPase Activity

“…Researchers have found several antiviral small compounds against PEDV in vitro . There are some compounds such as salinomycin ( Yuan et al, 2021 ), homoharringtonine ( Dong et al, 2018 ), and A77 1726 ( Li X. et al, 2020 ) preventing PEDV proliferation by affecting the host defense system. Many compounds inhibit PEDV replication by targeting PEDV 3CLpro, such as tomatidine ( Wang et al, 2020 ), hypericin ( Zhang Y et al, 2021 ), quercetin ( Li Z. et al, 2020 ), and GC376 ( Ye et al, 2020 ).…”