Journal
VIROLOGICA SINICA
Volume 38, Issue 2, Pages 296-308Publisher
KEAI PUBLISHING LTD
DOI: 10.1016/j.virs.2023.01.008
Keywords
Coronavirus; Porcine epidemic diarrhea virus (PEDV); Niclosamide (NIC); Antiviral; Virus entry; Endocytosis; Host-targeted antivirals
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In this study, a recombinant PEDV expressing renilla luciferase was used to screen potential anti-PEDV agents from an FDA-approved drug library, and four compounds were identified. Among them, niclosamide showed the most potent antiviral activity and the highest selectivity index, and it could efficiently inhibit viral RNA synthesis, protein expression, and viral progeny production. Additionally, a combination with other small molecule inhibitors of endosomal acidification enhanced the anti-PEDV effect of niclosamide.
Porcine epidemic diarrhea virus (PEDV), an enteropathogenic coronavirus, has catastrophic impacts on the global pig industry. However, there remain no effective drugs against PEDV infection. In this study, we utilized a re-combinant PEDV expressing renilla luciferase (PEDV-Rluc) to screen potential anti-PEDV agents from an FDA -approved drug library in Vero cells. Four compounds were identified that significantly decreased luciferase ac-tivity of PEDV-Rluc. Among them, niclosamide was further characterized because it exhibited the most potent antiviral activity with the highest selectivity index. It can efficiently inhibit viral RNA synthesis, protein expression and viral progeny production of classical and variant PEDV strains in a dose-dependent manner. Time of addition assay showed that niclosamide exhibited potent anti-PEDV activity when added simultaneously with or after virus infection. Furthermore, niclosamide significantly inhibited the entry stage of PEDV infection by affecting viral internalization rather than viral attachment to cells. In addition, a combination with other small molecule inhibitors of endosomal acidification enhanced the anti-PEDV effect of niclosamide in vitro. Taken together, these findings suggested that niclosamide is a novel antiviral agent that might provide a basis for the development of novel drug therapies against PEDV and other related pathogenic coronavirus infections.
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