scholarly journals Identification of two antiviral inhibitors targeting 3C-like serine/3C-like protease of porcine reproductive and respiratory syndrome virus and porcine epidemic diarrhea virus

2018 ◽  
Vol 213 ◽  
pp. 114-122 ◽  
Author(s):  
Yuejun Shi ◽  
Yingying Lei ◽  
Gang Ye ◽  
Limeng Sun ◽  
Liurong Fang ◽  
...  
Keyword(s):  
Porcine Epidemic Diarrhea Virus ◽  
Respiratory Syndrome Virus ◽  
Diarrhea Virus ◽  
Porcine Epidemic Diarrhea

PSVI-4 Efficacy of Medium Chain Fatty Acids and Fatty Acid-based Feed Additives as a Mitigation Strategy Against Porcine Epidemic Diarrhea Virus and Porcine Reproductive and Respiratory Syndrome Virus

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 216-217
Author(s):  
O L Harrison ◽  
G E Nichols ◽  
J T Gebhardt ◽  
Cassandra K Jones ◽  
Jason C Woodworth ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Porcine Epidemic Diarrhea Virus ◽  
Positive Control ◽  
Feed Additives ◽  
Feed Additive ◽  
Respiratory Syndrome Virus ◽  
Post Inoculation ◽  
Diarrhea Virus ◽  
Medium Chain ◽  
Porcine Epidemic Diarrhea

Abstract Recent research has demonstrated that swine viruses can be transmitted via feed. Chemical feed additives have been suggested for the mitigation of these viruses in complete feed. Therefore, the objective of this study was to evaluate the efficacy of a commercially available formaldehyde-based feed additive, medium chain fatty acid blend (MCFA), and commercially available fatty acid-based products for mitigation of porcine epidemic diarrhea virus (PEDV) and porcine reproductive and respiratory syndrome virus (PRRSV) in a feed matrix. Treatments consisted of: 1) non-treated positive control, 2) 0.33% commercial formaldehyde-based product (Sal Curb; Kemin Industries, Inc.; Des Moines, IA), 3) 0.5% MCFA blend (1:1:1 ratio of C6:0, C8:0, and C10:0, Sigma Aldrich, St. Louis, MO), 4) 0.25%, 5) 0.5%, or 6) 1% of commercial dry mono and diglyceride-based product (Furst Strike; Furst-McNess Company, Freeport, IL), 7) 0.25%, 8) 0.5%, or 9) 1% of commercial dry mono and diglyceride-based product (Furst Protect; Furst-McNess Company, Freeport, IL), 10) 0.25%, 11) 0.5%, or 12) 1% dry mono and diglyceride-based experimental product (Furst-McNess Company, Freeport, IL) with 3 replications/treatment. Treatments were applied to complete swine feed before inoculation with 106 TCID50/g of feed with PEDV or PRRSV. Post inoculation feed was held at ambient temperature for 24 h before being analyzed via qRT-PCR. The analyzed values represent the cycle threshold. Formaldehyde and MCFA decreased (P < 0.05) the detectable RNA of PEDV and PRRSV compared to all other treatments. Furst Strike, Furst Protect, and the experimental product did not significantly impact detectability of PEDV or PRRSV RNA. In conclusion, MCFA and formaldehyde treatments are effective at reducing detection of RNA from PEDV and PRRSV in feed.

scholarly journals Tomatidine inhibits porcine epidemic diarrhea virus replication by targeting 3CL protease

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Pengcheng Wang ◽  
Juan Bai ◽  
Xuewei Liu ◽  
Mi Wang ◽  
Xianwei Wang ◽  
...  
Keyword(s):  
Porcine Epidemic Diarrhea Virus ◽  
Economic Losses ◽  
Titration Calorimetry ◽  
Respiratory Syndrome Virus ◽  
Transmissible Gastroenteritis Virus ◽  
Diarrhea Virus ◽  
Infected Cells ◽  
Porcine Epidemic Diarrhea ◽  
3Cl Protease

Abstract Porcine epidemic diarrhea virus (PEDV) causes lethal diarrhea in suckling piglets, leading to severe economic losses worldwide. There is an urgent need to find new therapeutic methods to prevent and control PEDV. Not only is there a shortage of commercial anti-PEDV drugs, but available commercial vaccines fail to protect against highly virulent PEDV variants. We screened an FDA-approved library of 911 natural products and found that tomatidine, a steroidal alkaloid extracted from the skin and leaves of tomatoes, demonstrates significant inhibition of PEDV replication in Vero and IPEC-J2 cells in vitro. Molecular docking and molecular dynamics analysis predicted interactions between tomatidine and the active pocket of PEDV 3CL protease, which were confirmed by fluorescence spectroscopy and isothermal titration calorimetry (ITC). The inhibiting effect of tomatidine on 3CL protease was determined using cleavage visualization and FRET assay. Tomatidine-mediated blocking of 3CL protease activity in PEDV-infected cells was examined by western blot detection of the viral polyprotein in PEDV-infected cells. It indicates that tomatidine inhibits PEDV replication mainly by targeting 3CL protease. In addition, tomatidine also has antiviral activity against transmissible gastroenteritis virus (TGEV), porcine reproductive and respiratory syndrome virus (PRRSV), encephalo myocarditis virus (EMCV) and seneca virus A (SVA) in vitro. These results may be helpful in developing a new prophylactic and therapeutic strategy against PEDV and other swine disease infections.

PSVI-7 Evaluation of Feed Mitigant Efficacy for Control of Porcine Epidemic Diarrhea Virus and Porcine Reproductive and Respiratory Syndrome Virus When Inoculated Either Alone or Together

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 217-218
Author(s):  
Catherine Elijah ◽  
G E Nichols ◽  
J T Gebhardt ◽  
Cassandra K Jones ◽  
Jason C Woodworth ◽  
...  
Keyword(s):  
Porcine Epidemic Diarrhea Virus ◽  
Feed Additives ◽  
Respiratory Syndrome Virus ◽  
Diarrhea Virus ◽  
Additional Information ◽  
Qrt Pcr ◽  
Ct Value ◽  
Des Moines ◽  
Porcine Epidemic Diarrhea ◽  
Single Reaction

Abstract Research has demonstrated that swine feed can be a fomite for viral transmission and certain feed additives can effectively reduce viral contamination. However, additional information is needed to evaluate the efficacy of additives when feed is inoculated with more than one virus. The objective of this study was to evaluate the efficacy of two feed additives for mitigation of porcine epidemic diarrhea virus (PEDV) and porcine reproductive and respiratory syndrome virus (PRRSV) when inoculated individually or together. Feed additives included: 1) no treatment, 2) 0.33% commercial formaldehyde-based product (Sal Curb, Kemin Industries, Des Moines, IA), and 3) 0.50% medium chain fatty acids blend (MCFA; 1:1:1 ratio of C6:C8:C10, Sigma Aldrich, St. Louis, MO). Samples were inoculated with PEDV and PRRSV alone or together at an inoculation concentration of 106 TCID50/g for all viruses. Once inoculated, feed was stored at ambient temperature for 24-h before analyzed via qRT-PCR. For samples inoculated with PEDV or PRRSV alone, a qRT-PCR assay was used which was designed to detect PEDV or PRRSV nucleic acid. For co-inoculated samples, an assay was designed to independently detect both PEDV and PRRSV within a single reaction. For PEDV alone, there was marginally significant evidence that feed additives resulted in differences in cycle threshold (Ct) value (P = 0.052), but no evidence was observed for pairwise differences. For PRRSV alone, formaldehyde increased Ct compared to the untreated control and MCFA treatment (P < 0.05). For co-infection of PRRSV and PEDV, MCFA and formaldehyde increased Ct (P < 0.05) in comparison to non-treated feed. In summary, formaldehyde increased Ct values in feed when contaminated with PRRSV while both mitigants increased Ct value in feed when co-inoculated with PRRSV and PEDV.

scholarly journals Porcine Epidemic Diarrhea Virus nsp15 Antagonizes Interferon Signaling by RNA Degradation of TBK1 and IRF3

Viruses ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 599 ◽  
Author(s):  
Yang Wu ◽  
Hongling Zhang ◽  
Zhaorong Shi ◽  
Jianfei Chen ◽  
Mingwei Li ◽  
...  
Keyword(s):  
Porcine Epidemic Diarrhea Virus ◽  
Rna Degradation ◽  
Respiratory Syndrome Virus ◽  
Type I ◽  
Diarrhea Virus ◽  
Itraq Analysis ◽  
Porcine Epidemic Diarrhea ◽  
Innate Antiviral Response ◽  
Immune Pathway ◽  
Innate Immune Pathway

Porcine epidemic diarrhea virus (PEDV) causes a porcine disease associated with swine epidemic diarrhea. The type I interferon (IFN-I or IFN α/β) is a key mediator of innate antiviral response during virus infection. Different antagonistic strategies have been identified and determined as to how PEDV infection inhibits the host’s IFN responses to escape the host innate immune pathway, but the pathogenic mechanisms of PEDV infection are not fully elucidated. Our preliminary results revealed that endogenous TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3), the key components in the IFN signaling pathway were downregulated in PEDV infected IPEC-J2 cells by iTRAQ analysis. In this study, we screened nsp15 as the most important viral encoded protein involved in TBK1 and IRF3 reduction. Endoribonuclease (EndoU) activity has been well determined for coronavirus nsp15. Three residues (H226, H241, and K282) of PEDV nsp15 were identified as critical amino acids for PEDV EndoU but not D265, which was not well correlated with published results of other coronaviruses, such as severe acute respiratory syndrome virus (SARS-CoV). Moreover, PEDV nsp15 can directly degrade the RNA levels of TBK1 and IRF3 dependent on its EndoU activity to suppress IFN production and constrain the induction of IFN stimulated genes (ISGs), by which PEDV antagonizes the host innate response to facilitate its replication. Collectively, these results have confirmed that PEDV nsp15 was capable of subverting the IFN response by the RNA degradation of TBK1 and IRF3.

scholarly journals Identifying outbreaks of Porcine Epidemic Diarrhea virus through animal movements and spatial neighborhoods

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gustavo Machado ◽  
Carles Vilalta ◽  
Mariana Recamonde-Mendoza ◽  
Cesar Corzo ◽  
Montserrat Torremorell ◽  
...  
Keyword(s):  
Porcine Epidemic Diarrhea Virus ◽  
Animal Movements ◽  
Diarrhea Virus ◽  
Porcine Epidemic Diarrhea

scholarly journals Differential expression and correlation analysis of miRNA–mRNA profiles in swine testicular cells infected with porcine epidemic diarrhea virus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaoqian Zhang ◽  
Chang Li ◽  
Bingzhou Zhang ◽  
Zhonghua Li ◽  
Wei Zeng ◽  
...  
Keyword(s):  
Differential Expression ◽  
Porcine Epidemic Diarrhea Virus ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Bacterial Invasion ◽  
Sequencing Data ◽  
Diarrhea Virus ◽  
Comparison Groups ◽  
Porcine Epidemic Diarrhea

AbstractThe variant virulent porcine epidemic diarrhea virus (PEDV) strain (YN15) can cause severe porcine epidemic diarrhea (PED); however, the attenuated vaccine-like PEDV strain (YN144) can induce immunity in piglets. To investigate the differences in pathogenesis and epigenetic mechanisms between the two strains, differential expression and correlation analyses of the microRNA (miRNA) and mRNA in swine testicular (ST) cells infected with YN15, YN144, and mock were performed on three comparison groups (YN15 vs Control, YN144 vs Control, and YN15 vs YN144). The mRNA and miRNA expression profiles were obtained using next-generation sequencing (NGS), and the differentially expressed (DE) (p-value < 0.05) mRNA and miRNA were obtained using DESeq R package. mRNAs targeted by DE miRNAs were predicted using the miRanda algortithm. 8039, 8631 and 3310 DE mRNAs, and 36, 36, and 22 DE miRNAs were identified in the three comparison groups, respectively. 14,140, 15,367 and 3771 DE miRNA–mRNA (targeted by DE miRNAs) interaction pairs with negatively correlated expression patterns were identified, and interaction networks were constructed using Cytoscape. Six DE miRNAs and six DE mRNAs were randomly selected to verify the sequencing data by real-time relative quantitative reverse transcription polymerase chain reaction (qRT-PCR). Based on bioinformatics analysis, we discovered the differences were mostly involved in host immune responses and viral pathogenicity, including NF-κB signaling pathway and bacterial invasion of epithelial cells, etc. This is the first comprehensive comparison of DE miRNA–mRNA pairs in YN15 and YN144 infection in vitro, which could provide novel strategies for the prevention and control of PED.

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