Nucleocapsid proteins from other swine enteric coronaviruses differentially modulate PEDV replication

Sungsuwan, Suttipun; Jongkaewwattana, Anan; Jaru-Ampornpan, Peera

doi:10.1016/j.virol.2019.11.007

Cited by 23 publications

(22 citation statements)

References 66 publications

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“…The interaction between the N and M proteins facilitates the incorporation of the N protein-gRNA ribonucleoprotein complex into the forming viral particle (Kuo et al 2016 ). The N protein is also responsible for inducing endoplasmic reticulum (ER) stress, the prolongation of S phase, and the upregulation of interleukin 8 expression; it promotes the recovery of PEDV from infectious clones; and it increases the production of PEDV RNA and virions (Liwnaree et al 2019 ; Sungsuwan et al 2020 ; Xu et al 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Generation and functional analysis of single chain variable fragments (scFvs) targeting the nucleocapsid protein of Porcine epidemic diarrhea virus

Wang

Zhang

et al. 2022

Appl Microbiol Biotechnol

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Porcine epidemic diarrhea virus (PEDV) is the causative agent of porcine epidemic diarrhea, which can cause death in suckling piglets. Vaccines confer only partial protection against new mutant strains, whereas antibodies targeting virus-encoded proteins may be effective prophylactics. In this study, we constructed a recombinant single chain variable fragment (scFv) library from the spleens of two pigs immunized with a recombinant PEDV nucleocapsid (N) protein. Among the positive clones directed against PEDV N protein isolated from the library, four scFvs that showed higher affinity for N were functionally analyzed. These scFvs specifically bound to the PEDV N protein, but not to the transmissible gastroenteritis virus (TGEV) N protein. Their framework regions were highly conserved, whereas their complementarity-determining regions displayed clear diversity. An immunofluorescence assay showed the co-localization of the four scFvs with PEDV N protein in cells. They significantly suppressed PEDV replication, detected with reverse transcription (RT)-quantitative PCR (qPCR; P < 0.01). Two of them significantly reduced the viral titer at 48 hpi and 72 hpi ( P < 0.05). In addition, they observably suppressed the production of viral protein at 72 hpi. The expression of interferons, interferon regulatory factor 3 (IRF3), and IRF7 was assessed with RT-qPCR, which indicated that PEDV dramatically suppressed the transcription of interferon-λ1 and IRF7 and that the scFvs significantly upregulated their expression ( P < 0.05). These findings facilitated the investigation of the mechanism by which PEDV evaded the host immune response and suggested that these porcine scFvs were potential candidate agents for the prevention and treatment of porcine diarrhea caused by PEDV. Key points • Four scFvs targeting PEDV N protein were generated from porcine spleens • These scFvs co-localized with PEDV N protein and suppressed PEDV replication • These scFvs significantly upregulated IFN-λ1 expression Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s00253-021-11722-z.

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Section: Introductionmentioning

confidence: 99%

Generation and functional analysis of single chain variable fragments (scFvs) targeting the nucleocapsid protein of Porcine epidemic diarrhea virus

Wang

Zhang

et al. 2022

Appl Microbiol Biotechnol

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“…A recent study indicated that mixing of viral components during coinfection altered pathogenic outcomes or viral replication. For example, overexpression of TGEV N increased production of PEDV RNA and virions [ 22 ]; therefore, we inferred that one coinfecting virus might augment the proliferation of the other, leading to more-severe diarrheal disease. Notably, new strains are likely to emerge in cases of coinfection, such as the emergence of recombinant S-INDEL-variant PEDV [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Replicative capacity of four porcine enteric coronaviruses in LLC-PK1 cells

et al. 2021

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Enteric coronaviruses (CoVs) are major pathogens that cause diarrhea in piglets. To date, four porcine enteric CoVs have been identified: transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and HKU2-like porcine enteric alphacoronavirus (PEAV). In this study, we investigated the replicative capacity of these four enteric CoVs in LLC-PK1 cells, a porcine kidney cell line. The results showed that LLC-PK1 cells are susceptible to all four enteric CoVs, particularly to TGEV and PDCoV infections, indicating that LLC-PK1 cells can be applied to porcine enteric CoV research in vitro, particularly for coinfection studies.

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“…The coronavirus nucleocapsid phosphoprotein is a multifunctional structural protein; during virion assembly it interacts with the viral membrane and forms complexes with genomic RNA. The coronavirus nucleocapsid phosphoprotein plays an important role in coronavirus transcription and assembly as well as the coronavirus lifecycle [28][29][30][31][32][33][34]. The most potent identified compound, 1-[(2,4-dichlorophenyl)methyl]pyrazole-3,5-dicarboxylic acid], may inhibit any of its multifarious activities and functions during virion assembly; however, detailed studies are needed on the inhibitory effect of these compounds on the interaction of nucleocapsid phosphoprotein with the viral membrane, and formation of complexes with genomic RNA during SARS-CoV-2 transcription and virion assembly.…”

Section: Discussionmentioning

confidence: 99%

State-of-the-art tools to identify druggable protein ligand of SARS-CoV-2

Azeez¹,

Alhashim²,

Otaibi³

et al. 2020

aoms

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A b s t r a c t Introduction: The SARS-CoV-2 (previously 2019-nCoV) outbreak in Wuhan, China and other parts of the world affects people and spreads coronavirus disease 2019 (COVID-19) through human-to-human contact, with a mortality rate of > 2%. There are no approved drugs or vaccines yet available against SARS-CoV-2. Material and methods: State-of-the-art tools based on in-silico methods are a cost-effective initial approach for identifying appropriate ligands against SARS-CoV-2. The present study developed the 3D structure of the envelope and nucleocapsid phosphoprotein of SARS-CoV-2, and molecular docking analysis was done against various ligands. Results: The highest log octanol/water partition coefficient, high number of hydrogen bond donors and acceptors, lowest non-bonded interaction energy between the receptor and the ligand, and high binding affinity were considered for the best ligand for the envelope (mycophenolic acid: log P = 3.00; ΔG = -10.2567 kcal/mol; pKi = 7.713 μM) and nucleocapsid phosphoprotein (1-[(2,4-dichlorophenyl)methyl]pyrazole-3,5-dicarboxylic acid: log P = 2.901; ΔG = -12.2112 kcal/mol; pKi = 7.885 μM) of SARS-CoV-2. Conclusions: The study identifies the most potent compounds against the SARS-CoV-2 envelope and nucleocapsid phosphoprotein through state-ofthe-art tools based on an in-silico approach. A combination of these two ligands could be the best option to consider for further detailed studies to develop a drug for treating patients infected with SARS-CoV-2, COVID-19.

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Nucleocapsid proteins from other swine enteric coronaviruses differentially modulate PEDV replication

Cited by 23 publications

References 66 publications

Generation and functional analysis of single chain variable fragments (scFvs) targeting the nucleocapsid protein of Porcine epidemic diarrhea virus

Generation and functional analysis of single chain variable fragments (scFvs) targeting the nucleocapsid protein of Porcine epidemic diarrhea virus

Replicative capacity of four porcine enteric coronaviruses in LLC-PK1 cells

State-of-the-art tools to identify druggable protein ligand of SARS-CoV-2

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