Significant Inhibition of Porcine Epidemic Diarrhea Virus In Vitro by Remdesivir, Its Parent Nucleoside and β-D-N4-hydroxycytidine.

Abstract

Porcine epidemic diarrhea (PED) caused by porcine epidemic diarrhea virus (PEDV) is widespread in the world. In recent years, the increased virulence of the virus due to viral variations, has caused great economic losses to the pig industry in many countries. It is always worthy to find effective therapeutic methods for PED. As an important class of antivirals, nucleoside drugs which target viral polymerases have been applied in treating human viral infections for half a century. Herein, we evaluated the anti-PEDV potential of three broad-spectrum antiviral nucleoside analogs, remdesivir (RDV), its parent nucleoside (RDV-N) and β-d-N4-hydroxycytidine (NHC). Among them, RDV-N was the most active agent in Vero E6 cells with EC50 of 0.31 μmol/L, and more potent than RDV (EC50 = 0.74 μmol/L) and NHC (EC50 = 1.17 μmol/L). The activity of RDV-N was further confirmed using an indirect immuno-fluorescence assay. Moreover, RDV-N exhibited a good safety profile in cells and in mice. The high sequence similarity of the polymerase functional domains of PEDV with other five porcine coronaviruses indicated a broader antiviral spectrum for the three compounds. Generally, RDV-N is a promising broad-spectrum antiviral nucleoside, and it would be worthy to make some structural modifications to increase its oral bioavailability.