Abstract
Porcine epidemic diarrhea virus (PEDV), the etiology of porcine epidemic diarrhea (PED), continues to impose severe economic burdens on pig farms in China. The continuous emergence of new variant strains makes it difficult for vaccinated sows to provide protective immunity to piglets. Hence, there is an urgent need for efficacious therapeutic drugs in clinical practice. In the present study, the antiviral activity of GS-441524, a nucleoside analogue, against PEDV was evaluated. It can efficiently inhibit the proliferation of trypsin-dependent and trypsin-independent PEDVs in a dose-dependent manner, exhibiting greater efficacy against the trypsin-independent strain. GS-441524 can inhibit trypsin-independent PEDV proliferation in Vero cells with EC(50) and CC(50) values of 2.6 μM and 104.4 μM, respectively. As expected, GS-441524 exerts its inhibitory effect during the replication phase of the four stages of the PEDV proliferation cycle. Even at a high viral infection dose of MOI 0.5 or added 6 h post-viral infection, 20 μM GS-441524 can still effectively inhibit PEDV proliferation. These findings emphasize the potent antiviral activity of GS-441524 against PEDV, and its therapeutic efficacy on PEDV-infected piglets warrants further investigation.