Abstract

BackgroundPorcine epidemic diarrhea virus (PEDV) of the family Coronaviridae has caused substantial economic losses in the swine husbandry industry. There’s currently no specific drug available for treatment of coronaviruses or PEDV.MethodIn the current study, we use coronavirus PEDV as a model to study antiviral agents. Briefly, a fusion inhibitor tHR2, recombinant lentivirus-delivered shRNAs targeted to conserved M and N sequences, homoharringtonine (HHT), and hydroxychloroquine (HCQ) were surveyed for their antiviral effects.ResultsTreatment with HCQ at 50 μM and HHT at 150 nM reduced virus titer in TCID50 by 30 and 3.5 fold respectively, and the combination reduced virus titer in TCID50 by 200 fold.ConclusionOur report demonstrates that the combination of HHT and HCQ exhibited higher antiviral activity than either HHT or HCQ exhibited. The information may contribute to the development of antiviral strategies effective in controlling PEDV infection.

Highlights

  • Porcine epidemic diarrhea virus (PEDV) belongs to the subfamily Coronavirinae of the family Coronaviridae, which causes epidemic diarrhea in swine, and was first reported in 1971 in the United Kingdom and was soon identified in many European and Asian countries [1]

  • Dual short hairpin RNA (shRNA)-expressing plasmid shRNA-MN was constructed To suppress the replication of PEDV, Vero cells were transfected with shRNA-expressing plasmid targeting the M or N of PEDV, or shRNA targeting the M and N genes

  • For the dual shRNA expression vector, two shRNAs respectively targeting M and N were incorporated into one vector, pGPU6/GFP/Neo-shRNA-MN, which carries two expression cassettes each containing a U6 promoter

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Summary

Introduction

Porcine epidemic diarrhea virus (PEDV) belongs to the subfamily Coronavirinae of the family Coronaviridae, which causes epidemic diarrhea in swine, and was first reported in 1971 in the United Kingdom and was soon identified in many European and Asian countries [1]. The PEDV is an enveloped, positive-sense single-strand RNA virus. The viral genome is approximately 28 kb and includes more than seven open reading frames (ORF) that encode 4 structural proteins, including spike glycoprotein (S), nucleocapsid protein (N), membrane protein (M), and envelope protein (E), 15 non-structural proteins (NSP), and accessory protein ORF3 [1]. Porcine epidemic diarrhea virus (PEDV) of the family Coronaviridae has caused substantial economic losses in the swine husbandry industry. There’s currently no specific drug available for treatment of coronaviruses or PEDV

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