Porcine Epidemic Diarrhea Virus Is Inhibited by GS-441524 During an In Vitro Infection

TL;DR

GS-441524, a nucleoside analogue, effectively inhibits the growth of Porcine Epidemic Diarrhea Virus in laboratory tests, showing promise as a potential treatment.

Contribution

GS-441524 demonstrates potent antiviral activity against both trypsin-dependent and trypsin-independent PEDV strains in vitro.

Findings

GS-441524 inhibits PEDV proliferation in a dose-dependent manner with EC50 of 2.6 μM and CC50 of 104.4 μM.

The drug is more effective against trypsin-independent PEDV strains and works during the replication phase of the virus.

Even at high infection doses or delayed administration, GS-441524 remains effective in inhibiting PEDV.

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 EC50 and CC50 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.

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