Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus that can cause acute diarrhea, vomiting, dehydration, and high mortality of newborn piglets, leading to huge economic losses to the world pig industry. Given the limited efficacy of current PEDV vaccines, there is an urgent need for the development of antiviral drugs. In this study, the antiviral effects of 17 synthesized indole alkaloid derivatives against PEDV were investigated. It was observed that indole alkaloid derivative no. 14 exhibited significant inhibition of PEDV replication in a dose-dependent manner. Furthermore, time-of-addition assays and quantitative real-time PCR (QPCR) showed that delayed administration of this compound resulted in a weaker inhibitory effect on PEDV compared to early treatment. Mechanistic analysis revealed that this compound exerts its inhibitory effects during the entry stage of the PEDV life cycle. This study demonstrates the anti-PEDV effects of indole alkaloid derivative no. 14, suggesting its potential as a candidate drug for treating PEDV infections.
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