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Antiviral Compounds Against Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus

Author:
Deejai, Nipaporn, Roshorm, Yaowaluck Maprang, Kubera, Anchanee
Source:
Animal biotechnology 2017 v.28 no.2 pp. 120-130
ISSN:
1532-2378
Subject:
Escherichia coli, Porcine epidemic diarrhea virus, RNA-binding proteins, amino acid sequences, antiviral agents, antiviral properties, biotin, databases, diarrhea, drugs, genes, glutathione, inhibitory concentration 50, models, nucleocapsid, nucleocapsid proteins, swine, viruses
Abstract:
Porcine epidemic diarrhea (PED) is a severe diarrhea disease in swine that is caused by porcine epidemic diarrhea virus (PEDV). Nucleocapsid (N) protein is the RNA-binding protein of PEDV, which plays an important role for virus life cycle. The aim of this research was to screen and characterize the compounds that could inhibit the activity of PEDV N protein. The gene encoding PEDV N protein obtained from PEDV Thai isolate was cloned and expressed in E. coli. Its amino acid sequence was employed to generate the three dimensional structure by homology modeling. There were 1,286 compounds of FDA-approved drug database that could virtually bind to the RNA-binding region of N protein. Three compounds, trichlormethiazide, D-(+) biotin, and glutathione successfully bound to the N protein, in vitro, with the IC ₅₀ at 8.754 mg/mL, 0.925 mg/mL, and 2.722 mg/mL. Antiviral activity in PEDV-infected Vero cells demonstrated that the effective concentration of trichlormethiazide, D-(+) biotin, and glutathione in inhibiting PEDV replication were 0.094, 0.094 and 1.5 mg/mL. This study demonstrated a strategy applied for discovery of antiviral agents capable of inhibiting PEDV N protein and PEDV replication. The compounds identified here exhibited a potential use as therapeutic agents for controlling PEDV infection.
Agid:
5662561