Dong Shijuan, Sun Rujing, Chen Bingqing, Si Fusheng, Li Chunhua, Zhang Daojing, Yu Ruisong, Liu Huili
Institute of Animal Science and Veterinary Medicine, Shanghai Key Laboratory of Agricultural Genetics and Breeding, Shanghai Engineering Research Center of Breeding Pig, Shanghai Academy of Agricultural Sciences (SAAS), Shanghai 201106, China.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology (ECUST), Shanghai 200237, China.
Microorganisms. 2025 May 8;13(5):1089. doi: 10.3390/microorganisms13051089.
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 and CC 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.
猪流行性腹泻病毒(PEDV)是猪流行性腹泻(PED)的病原体,持续给中国的养猪场带来沉重的经济负担。新变异毒株的不断出现使得接种疫苗的母猪难以给仔猪提供保护性免疫。因此,临床实践中迫切需要有效的治疗药物。在本研究中,评估了核苷类似物GS-441524对PEDV的抗病毒活性。它能以剂量依赖的方式有效抑制依赖胰蛋白酶和不依赖胰蛋白酶的PEDV的增殖,对不依赖胰蛋白酶的毒株显示出更高的疗效。GS-441524能抑制Vero细胞中不依赖胰蛋白酶的PEDV增殖,其半数有效浓度(EC)和半数细胞毒性浓度(CC)分别为2.6 μM和104.4 μM。正如预期的那样,GS-441524在PEDV增殖周期四个阶段的复制期发挥其抑制作用。即使在高病毒感染复数(MOI)为0.5或在病毒感染后6小时添加的情况下,20 μM的GS-441524仍能有效抑制PEDV增殖。这些发现强调了GS-441524对PEDV具有强大的抗病毒活性,其对PEDV感染仔猪的治疗效果值得进一步研究。