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1.
Bioorg Chem ; 146: 107322, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38555797

RESUMO

Porcine Delta Coronavirus (PDCoV) infection can induce serious dehydration, diarrhea and even death of piglets, which has caused huge losses to the breeding industry. PDCoV has been reported to have the potential for cross species transmission, and even reports of infecting humans have emerged. At present, there are still no effective prevention and control measures for PDCoV. In this study, we have designed and synthesized a series of unreported Dihydropteridone derivatives. All of these compounds were evaluated for the against PDCoV in vivo and in vitro for the first time. In this study, antiviral activity (17.34 ± 7.20 µM) and low cytotoxicity (>800 µM) was found in compound W8. Compound W8 exerts antiviral effect on PDCoV by inhibiting cell apoptosis and inflammatory factors caused by virus infection in vitro. In addition, lung and small intestinal lesions caused by PDCoV infection in mice could be significantly reduced by compound W8. These findings highlight the potential of compound W8 as a valuable therapeutic option against PDCoV infection, and lay a foundation for further research and development in this field.


Assuntos
Infecções por Coronavirus , Coronavirus , Sulfonamidas , Suínos , Animais , Humanos , Camundongos , Intestino Delgado , Antivirais/farmacologia
2.
J Med Virol ; 94(12): 5723-5738, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35927214

RESUMO

Porcine deltacoronavirus (PDCoV) is a novel coronavirus that causes diarrhea in suckling piglets and has the potential for cross-species transmission, posing a threat to animal and human health. However, the susceptibility profile of different species of mice to PDCoV infection and its evolutionary characteristics are still unclear. In the current study, we found that BALB/c and Kunming mice are susceptible to PDCoV. Our results showed that there were obvious lesions in intestinal and lung tissues from the infected mice. PDCoV RNAs were detected in the lung, kidney, and intestinal tissues from the infected mice of both strains, and there existed wider tissue tropism in the PDCoV-infected BALB/c mice. The RNA and protein levels of aminopeptidase N from mice were relatively high in the kidney and intestinal tissues and obviously increased after PDCoV infection. The viral-specific IgG and neutralizing antibodies against PDCoV were detected in the serum of infected mice. An interesting finding was that two key amino acid mutations, D138H and Q641K, in the S protein were identified in the PDCoV-infected mice. The essential roles of these two mutations for PDCoV-adaptive evolution were confirmed by cryo-electron microscope structure model analysis. The evolutionary characteristics of PDCoV among Deltacoronaviruses (δ-CoVs) were further analyzed. δ-CoVs from multiple mammals are closely related based on the phylogenetic analysis. The codon usage analysis demonstrated that similar codon usage patterns were used by most of the mammalian δ-CoVs at the global codon, synonymous codon, and amino acid usage levels. These results may provide more insights into the evolution, host ranges, and cross-species potential of PDCoV.


Assuntos
COVID-19 , Doenças dos Suínos , Aminoácidos , Animais , Anticorpos Neutralizantes , Antígenos CD13/genética , Antígenos CD13/metabolismo , Deltacoronavirus , Humanos , Imunoglobulina G , Mamíferos/metabolismo , Camundongos , Filogenia , RNA , Suínos
3.
J Med Virol ; 94(9): 4393-4405, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35560068

RESUMO

A new series of butene lactone derivatives were designed according to an influenza neuraminidase target and their antiviral activities against H1N1 infection of Madin-Darby canine kidney cells were evaluated. Among them, a compound that was given the name M355 was identified as the most potent against H1N1 (EC50 = 14.7 µM) with low toxicity (CC50 = 538.13 µM). It also visibly reduced the virus-induced cytopathic effect. Time-of-addition analysis indicated that H1N1 was mostly suppressed by M355 at the late stage of its infectious cycle. M355 inhibited neuraminidase in a dose-dependent fashion to a similar extent as oseltamivir, which was also indicated by a computer modeling experiment. In a mouse model, lung lesions and virus load were reduced and the expression of nucleoprotein was moderated by M355. The enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction analyses revealed that the levels of interferon-γ, interferon regulatory factor-3, Toll-like receptor-3, tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and IL-8 were downregulated in the M355-treated groups, whereas the levels of IL-10 and IL-13 were upregulated. Similarly, IgG was found to be increased in infected mice plasma. These results demonstrate that M355 inhibit the expression of H1N1 in both cellular and animal models. Thus, M355 has the potential to be effective in the treatment of influenza A virus infection.


Assuntos
Alcenos , Antivirais , Vírus da Influenza A Subtipo H1N1 , Lactonas , Infecções por Orthomyxoviridae , Alcenos/farmacologia , Animais , Antivirais/farmacologia , Cães , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Lactonas/farmacologia , Células Madin Darby de Rim Canino , Camundongos , Neuraminidase , Infecções por Orthomyxoviridae/tratamento farmacológico
4.
Bioprocess Biosyst Eng ; 44(3): 473-482, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33051705

RESUMO

Interferon α (IFN-α) plays a crucial role in the host's immune response. In this study, the amino acid sequence of porcine interferon α (PoIFN-α) was analyzed. Seven substitutions, S38F, H40Q, F43L, N78D, Y86C, S151A, and R156T, were mutated and obtained by aligning the sequences of PoIFN-α subtypes. The PoIFN-α mutants were designed, expressed, and purified in E. coli. The antiviral activities of these PoIFN-αs were measured in Vero and swine testis cells against vesicular stomatitis virus (VSV). Their inhibitory abilities on pseudorabies virus (PRV) were also examined. Commercial PoIFN-α was used as a control. We found the ideal inducer concentration of isopropyl ß-D-thiogalactoside was 1 mM, and the best time-point for induction was 8 h. The PoIFN-α mutant named PoIFN-α-156s had the highest antiviral activity, which was about 200-fold more than that of PoIFN-α. PoIFN-α-156s could inhibit VSV and PRV replication in a dose-dependent manner in vitro. The half-life of PoIFN-α-156s was longer than that of PoIFN-α in mice, and the effective antiviral action was higher than PoIFN-α. Animal experiments showed that PoIFN-α-156s could decrease the viral load after infection with VSV. Overall, these results suggest that recombinant PoIFN-α-156s has the ability of antivirus, and is feasible for veterinary clinical applications and fundamental research.


Assuntos
Substituição de Aminoácidos , Escherichia coli , Interferon-alfa , Mutação de Sentido Incorreto , Animais , Chlorocebus aethiops , Escherichia coli/genética , Escherichia coli/metabolismo , Interferon-alfa/biossíntese , Interferon-alfa/química , Interferon-alfa/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Suínos , Células Vero
5.
Virol J ; 17(1): 163, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097081

RESUMO

BACKGROUND: Transmissible gastroenteritis virus (TGEV) causes enteric infection in piglets, characterized by vomiting, severe diarrhea and dehydration, and the mortality in suckling piglets is often high up to 100%. Vaccination is an effective measure to control the disease caused by TGEV. METHODS: In this study, cell-cultured TGEV HN-2012 strain was inactivated by formaldehyde (FA), ß-propiolactone (BPL) or binaryethylenimine (BEI), respectively. Then the inactivated TGEV vaccine was prepared with freund's adjuvant, and the immunization effects were evaluated in mice. The TGEV-specific IgG level was detected by ELISA. The positive rates of CD4+, CD8+, CD4+IFN-γ+, CD4+IL-4+ T lymphocytes were detected by flow cytometry assay. Lymphocyte proliferation assay and gross pathology and histopathology examination were also performed to assess the three different inactivating reagents in formulating TGEV vaccine. RESULTS: The results showed that the TGEV-specific IgG level in FA group (n = 17) was earlier and stronger, while the BEI group produced much longer-term IgG level. The lymphocyte proliferation test demonstrated that the BEI group had a stronger ability to induce spleen lymphocyte proliferation. The positive rates of CD4+ and CD8+ T lymphocyte subsets of peripheral blood lymphocyte in BEI group was higher than that in FA group and BPL groups by flow cytometry assay. The positive rate of CD4+IFN-γ+ T lymphocyte subset was the highest in the BPL group, and the positive rate of CD4+IL-4+ T lymphocyte subset was the highest in the FA group. There were no obvious pathological changes in the vaccinated mice and the control group after the macroscopic and histopathological examination. CONCLUSIONS: These results indicated that all the three experimental groups could induce cellular and humoral immunity, and the FA group had the best humoral immunity effect, while the BEI group showed its excellent cellular immunity effect.


Assuntos
Anticorpos Antivirais/sangue , Gastroenterite Suína Transmissível/prevenção & controle , Indicadores e Reagentes/farmacologia , Vírus da Gastroenterite Transmissível/efeitos dos fármacos , Vacinas Virais/imunologia , Inativação de Vírus/efeitos dos fármacos , Animais , Feminino , Imunidade Celular , Imunidade Humoral , Imunoglobulina G/sangue , Indicadores e Reagentes/classificação , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Suínos , Linfócitos T/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/administração & dosagem
6.
Cell Mol Biol Lett ; 24: 36, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31164908

RESUMO

Common environmental pollutants and drugs encountered in everyday life can cause toxic damage to the body through oxidative stress, inflammatory stimulation, induction of apoptosis, and inhibition of energy metabolism. Silent information regulator 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent deacetylase, is a member of the evolutionarily highly conserved Sir2 (silent information regulator 2) superprotein family, which is located in the nucleus and cytoplasm. It can deacetylate protein substrates in various signal transduction pathways to regulate gene expression, cell apoptosis and senescence, participate in the process of neuroprotection, energy metabolism, inflammation and the oxidative stress response in living organisms, and plays an important role in toxic damage caused by toxicants and in the process of SIRT1 activator/inhibitor antagonized toxic damage. This review summarizes the role that SIRT1 plays in toxic damage caused by toxicants via its interactions with protein substrates in certain signaling pathways.


Assuntos
Transdução de Sinais , Sirtuína 1/metabolismo , Toxinas Biológicas/toxicidade , Animais , Humanos , Modelos Biológicos , Transdução de Sinais/efeitos dos fármacos
7.
Nanomedicine ; 14(4): 1201-1212, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29501635

RESUMO

Inactivated transmissible gastroenteritis virus (TGEV) vaccines are widely used in swine herds in China. These are limited, however, by the need to elicit both humoral and cellular immunity, as well as the efficiency of adjuvants. In this study, a 70-nm nano silicon particle was applied with inactivated TGEV vaccine in mice, and its immune-enhancing effects and mechanism of action investigated. We found that nano silicon applied with inactivated TGEV vaccine induced high antibody titers, increase IL-6, TNF-α and IFN-γ expression, and stimulate CD3+ T cell proliferation with a high CD4+/CD8+ T lymphocyte ratio. Nano silicon could quickly activate innate and adaptive immunity by stimulating Toll-like receptor signaling pathways, indicating that the nano silicon adjuvant enhanced long-term humoral and early cellular immune responses when combined with inactivated TGEV vaccine. Nano silicon could be considered for use as an antigen- carrier and adjuvant for veterinary vaccines.


Assuntos
Imunidade Celular/imunologia , Imunidade Humoral/imunologia , Silício/química , Vírus da Gastroenterite Transmissível/imunologia , Vacinas de DNA/imunologia , Vacinas de DNA/uso terapêutico , Adjuvantes Imunológicos , Animais , Linhagem Celular , Ensaio de Imunoadsorção Enzimática , Gastroenterite/imunologia , Gastroenterite/prevenção & controle , Interferon gama/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Suínos , Fator de Necrose Tumoral alfa/metabolismo
8.
Microbiol Spectr ; 12(6): e0391423, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38742903

RESUMO

Porcine parvovirus (PPV) is one of the most important pathogens that cause reproductive failure in pigs. However, the pathogenesis of PPV infection remains unclear. Proteomics is a powerful tool to understand the interaction between virus and host cells. In the present study, we analyzed the proteomics of PPV-infected PK-15 cells. A total of 32 and 345 proteins were differentially expressed at the early and replication stages, respectively. Subsequent gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed these differentially expressed proteins were significantly enriched in pathways including toll-like receptor signaling pathway, tumor necrosis factor signaling pathway, and viral carcinogenesis. The expression of poly (rC) binding protein 1 (PCBP1) was observed to decrease after PPV infection. Overexpressed or silenced PCBP1 expression inhibited or promoted PPV infection. Our studies established a foundation for further exploration of the multiplication mechanism of PPV. IMPORTANCE: Porcine parvovirus (PPV) is a cause of reproductive failure in the swine industry. Our knowledge of PPV remains limited, and there is no effective treatment for PPV infection. Proteomics of PPV-infected PK-15 cells was conducted to identify differentially expressed proteins at 6 hours post-infection (hpi) and 36 hpi. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that various pathways participate in PPV infection. Poly (rC) binding protein 1 was confirmed to inhibit PPV replication, which provided potential targets for anti-PPV infection. Our findings improve the understanding of PPV infection and pave the way for future research in this area.


Assuntos
Infecções por Parvoviridae , Parvovirus Suíno , Proteômica , Proteínas de Ligação a RNA , Doenças dos Suínos , Replicação Viral , Parvovirus Suíno/genética , Parvovirus Suíno/fisiologia , Animais , Suínos , Linhagem Celular , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Infecções por Parvoviridae/virologia , Infecções por Parvoviridae/metabolismo , Infecções por Parvoviridae/veterinária , Doenças dos Suínos/virologia , Doenças dos Suínos/metabolismo , Doenças dos Suínos/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo
9.
Biosci Rep ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712547

RESUMO

Porcine deltacoronavirus (PDCoV) is an newly emerged enteropathogenic coronavirus, mainly causing diarrhea in suckling piglets, and also has the potential for cross-species transmission. However, there are no effective vaccines or specific therapeutic agents for PDCoV. This study investigates the antiviral properties of baicalein against PDCoV infection in swine testicle cells (ST). It reveals that baicalein exerts a dose-dependent inhibitory effect on PDCoV replication, primarily targeting the replication stage of the viral infection by impeding viral RNA and protein synthesis. Furthermore, treatment with baicalein leads to reduced phosphorylation of PI3K, AKT, and NF-κB p65 proteins, along with decreased mRNA levels of pro-inflammatory cytokines (IL-1ß, IL-6, IL-8, and TNF-α). These results signify that PDCoV replication is inhibited through the inhibition of the PI3K-Akt-NF-κB protein signaling pathway, thereby suppressing the inflammatory response. In conclusion, it underscores the potential of baicalein as a therapeutic candidate for treating PDCoV infection.

10.
Virus Genes ; 46(3): 479-86, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23468229

RESUMO

In the present study, Torque teno sus viruses (TTSuVs) were detected in tissue and blood samples obtained from domestic pigs in central China, and complete genomes of TTSuVs were characterized. A total of three tissue samples (3/20, 15 %) from post-weaning multisystemic wasting syndrome-affected pigs and 30 blood samples (30/40, 75 %) from healthy pigs were positive for Torque teno sus virus 1 (TTSuV1) and/or 2 (TTSuV2). Two TTSuV strains (TTV1Hn54 and TTV2Hn93) comprising 2,794 and 2,875 nucleotides, respectively, each had four open reading frames (ORFs) and the untranslated region with TATA box and GC-rich region. Genomic sequence of TTV2Hn93 strain was unique in length compared with other TTSuV2 genomic sequences. Interestingly, three rolling-circle replication (RCR) motif-IIIs (YXXK) which were located at amino acid (aa) position 166-169, 328-331, and 379-382, respectively, were found in the ORF1 of TTV1Hn54. Two RCR motif-IIIs (YXXK) at the aa position 105-108 and 480-483 respectively, were also identified in the ORF1 of TTV2Hn93. Phylogenetic tree based on complete genomes showed that TTV1Hn54 strain was designated into type TTSuV1b and had a slight high sequence identity of 91 % with the Canada strain (JQ120664). TTV2Hn93 strain was classified into subtype TTSuV2d and shared the highest identity (97 %) with the Spain strain (GU570207).


Assuntos
Circovirus/genética , DNA Viral/química , DNA Viral/genética , Genoma Viral , Síndrome Definhante Multissistêmico de Suínos Desmamados/virologia , Regiões 5' não Traduzidas , Motivos de Aminoácidos , Estruturas Animais/virologia , Animais , Sangue/virologia , China , Circovirus/isolamento & purificação , Análise por Conglomerados , Dados de Sequência Molecular , Fases de Leitura Aberta , Filogenia , Análise de Sequência de DNA , Sus scrofa , Suínos , TATA Box
11.
Int J Biol Macromol ; 252: 126113, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37541479

RESUMO

Porcine deltacoronavirus (PDCoV) is a global epidemic enteropathogenic coronavirus that mainly infects piglets, and causes huge losses to the pig industry. However, there are still no commercial vaccines available for PDCoV prevention and controlment. Receptor-binding domain (RBD) is located at the S1 subunit of PDCoV and is the major target for developing viral inhibitor and vaccine. In this study, the characteristics of the RBD were analyzed by bioinformatic tools, and codon optimization was performed to efficiently express the PDCoV-RBD protein in the insect baculovirus expression system. The purified PDCoV-RBD protein was obtained and fully emulsified with CPG2395 adjuvant, aqueous adjuvant and Al(OH)3 adjuvant, respectively, to develop vaccines. The humoral and cellular immune responses were assessed on mice. The results showed that both the RBD/CPG2395 and RBD/aqueous adjuvant could induce stronger immune responses in mice than that of RBD/Al(OH)3. In addition, the PDCoV challenge infection was conducted and the RBD/CPG2395 could provide better protection against PDCoV in mice. Our study showed that the RBD protein has good antigenicity and can be used as a protective antigen, which provided a basis for the development of the PDCoV vaccine.


Assuntos
Coronavirus , Vacinas , Animais , Suínos , Camundongos , Proteínas de Transporte , Coronavirus/genética , Códon/genética , Baculoviridae/genética
12.
Sci Adv ; 9(24): eadf4098, 2023 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-37315148

RESUMO

Viral infections continue to threaten human health. It remains a major challenge to efficiently inhibit viral infection while avoiding secondary injury. Here, we designed a multifunctional nanoplatform (termed as ODCM), prepared by oseltamivir phosphate (OP)-loaded polydopamine (PDA) nanoparticles camouflaged by the macrophage cell membrane (CM). OP can be efficiently loaded onto the PDA nanoparticles through the π-π stacking and hydrogen bonding interactions with a high drug-loading rate of 37.6%. In particular, the biomimetic nanoparticles can accumulate actively in the damaged lung model of viral infection. At the infection site, PDA nanoparticles can consume excess reactive oxygen species and be simultaneously oxidized and degraded to achieve controlled release of OP. This system exhibits enhanced delivery efficiency, inflammatory storm suppression, and viral replication inhibition. Therefore, the system exerts outstanding therapeutic effects while improving pulmonary edema and protecting lung injury in a mouse model of influenza A virus infection.


Assuntos
Antivirais , Nanomedicina , Humanos , Animais , Camundongos , Antivirais/farmacologia , Oseltamivir , Indóis/farmacologia
13.
Animals (Basel) ; 13(21)2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37958075

RESUMO

Haemophilus parasuis (H. parasuis, HPS) is a prominent pathogenic bacterium in pig production. Its infection leads to widespread fibrinous inflammation in various pig tissues and organs, often in conjunction with various respiratory virus infections, and leads to substantial economic losses in the pig industry. Therefore, the rapid diagnosis of this pathogen is of utmost importance. In this study, we used recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats (CRISPR) technology to establish a convenient detection and analysis system for H. parasuis that is fast to detect, easy to implement, and accurate to analyze, known as RPA-CRISPR/Cas12a analysis. The process from sample to results can be completed within 1 h with high sensitivity (0.163 pg/µL of DNA template, p < 0.05), which is 104 -fold higher than the common PCR method. The specificity test results show that the RPA-CRISPR/Cas12a analysis of H. parasuis did not react with other common pig pathogens, including Streptococcus suis type II and IX, Actinobacillus pleuropneumoniae, Escherichia coli, Salmonella, Streptococcus suis, and Staphylococcus aureus (p < 0.0001). The RPA-CRISPR/Cas12a assay was applied to 15 serotypes of H. parasuis clinical samples through crude extraction of nucleic acid by boiling method, and all of the samples were successfully identified. It greatly reduces the time and cost of nucleic acid extraction. Moreover, the method allows results to be visualized with blue light. The accurate and convenient detection method could be incorporated into a portable format as point-of-care (POC) diagnostics detection for H. parasuis at the field level.

14.
Viruses ; 14(4)2022 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-35458502

RESUMO

Porcine deltacoronavirus (PDCoV) mainly causes severe diarrhea and intestinal pathological damage in piglets and poses a serious threat to pig farms. Currently, no effective reagents or vaccines are available to control PDCoV infection. Single-chain fragment variable (scFv) antibodies can effectively inhibit virus infection and may be a potential therapeutic reagent for PDCoV treatment. In this study, a porcine phage display antibody library from the peripheral blood lymphocytes of piglets infected with PDCoV was constructed and used to select PDCoV-specific scFv. The library was screened with four rounds of biopanning using the PDCoV N protein, and the colony with the highest affinity to the PDCoV N protein was obtained (namely, N53). Then, the N53-scFv gene fragment was cloned into plasmid pFUSE-hIgG-Fc2 and expressed in HEK-293T cells. The scFv-Fc antibody N53 (namely, scFv N53) was purified using Protein A-sepharose. The reactive activity of the purified antibody with the PDCoV N protein was confirmed by indirect enzyme-linked immunosorbent assay (ELISA), western blot and indirect immunofluorescence assay (IFA). Finally, the antigenic epitopes that the scFv N53 recognized were identified by a series of truncated PDCoV N proteins. The amino acid residues 82GELPPNDTPATTRVT96 of the PDCoV N protein were verified as the minimal epitope that can be recognized by the scFv-Fc antibody N53. In addition, the interaction between the scFv-Fc antibody N53 and the PDCoV N protein was further analyzed by molecule docking. In conclusion, our research provides some references for the treatment and prevention of PDCoV.


Assuntos
Bacteriófagos , Infecções por Coronavirus , Anticorpos de Cadeia Única , Doenças dos Suínos , Animais , Anticorpos Antivirais , Deltacoronavirus , Epitopos , Proteínas do Nucleocapsídeo/genética , Anticorpos de Cadeia Única/genética , Suínos , Tecnologia
15.
Eur J Med Chem ; 232: 114189, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35196598

RESUMO

Influenza is a century-old disease that continues to baffle humans by its frequently changing nature, seasonal epidemics, and occasional pandemics. Approximately 9% of the world's population is infected by the influenza virus annually. The emergence of novel strains because of rapid mutations as well as interspecies disease contamination, limits the efficiency of strain-specific vaccines. Anti-influenza drugs such as neuraminidase inhibitors, M2 ion channel inhibitors, etc. have become the first line of defense in prophylaxis and early containment of the disease. But the growing drug resistance due to drug-induced selective pressure has also limited the efficacy of those drugs. Because we can't predict the next strain types, their virulence, or the severity of the next epidemic/pandemic caused by influenza virus, we ought to gear up for the development of novel anti-influenza drugs with a broad spectrum of reactivity against all strains and subtypes, better bioavailability, easier administrative pathways, and lesser adverse effects. Various new compounds with each having significantly different target molecules and pharmacologic activity have shown potential against influenza virus strains in laboratory situations as well as clinical trials. We should also consider combination therapy to boost the efficacy of existing drugs. This review is aiming to succinctly document the recent signs of progress regarding anti-influenza drugs both in the market and under investigation.


Assuntos
Influenza Humana , Orthomyxoviridae , Antivirais/farmacologia , Antivirais/uso terapêutico , Inibidores Enzimáticos/farmacologia , Guanidinas/farmacologia , Humanos , Influenza Humana/tratamento farmacológico , Neuraminidase
16.
Viruses ; 14(8)2022 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-36016307

RESUMO

In late 2011, severe pseudorabies (PR) outbreaks occurred among swine herds vaccinated with the Bartha-K61 vaccine in many provinces of China, causing enormous economic losses for the pork industry. To understand the epidemic profile and genetic characteristics of the pseudorabies virus (PRV), a total of 35,796 serum samples were collected from 1090 pig farms of different breeding scales between 2019 and 2021 in the Henan province where swine had been immunized with the Bartha-K61 vaccine, and PRV glycoprotein E (gE)-specific antibodies were detected using an enzyme-linked immunosorbent assay (ELISA). The results reveal that the overall positive rate for PRV gE antibodies was 20.33% (7276/35,796), which decreased from 25.00% (2596/10,385) in 2019 to 16.69% (2222/13,315) in 2021, demonstrating that PR still existed widely in pig herds in the Henan province but displayed a decreasing trend. Further analysis suggested that the PRV-seropositive rate may be associated with farm size, farm category, quarter, region and the cross-regional transportation of livestock. Moreover, the gE gene complete sequences of 18 PRV isolates were obtained, and they shared a high identity (97.1-100.0%) with reference strains at the nucleotide level. Interestingly, the phylogenetic analysis based on the gE complete sequences found that there were both classical strains and variant strains in pig herds. The deduced amino acid sequence analysis of the gE gene showed that there were unique amino acids in the classical strains, the variant strains and genotype Ⅱ strains. This study provides epidemiological data that could be useful in the prevention of pseudorabies in Henan, China, and this finding contributed to our understanding of the epidemiology and evolution of PRV.


Assuntos
Herpesvirus Suídeo 1 , Pseudorraiva , Doenças dos Suínos , Animais , China/epidemiologia , Surtos de Doenças/veterinária , Filogenia , Suínos
17.
Front Immunol ; 13: 952852, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059492

RESUMO

There are no licensed therapeutics or vaccines available against porcine delta coronavirus (PDCoV) to eliminate its potential for congenital disease. In the absence of effective treatments, it has led to significant economic losses in the swine industry worldwide. Similar to the current coronavirus disease 2019 (COVID-19) pandemic, PDCoV is trans-species transmissible and there is still a large desert for scientific exploration. We have reported that selenomethionine (SeMet) has potent antiviral activity against PDCoV. Here, we systematically investigated the endogenous immune mechanism of SeMet and found that STAT3/miR-125b-5p-1/HK2 signalling is essential for the exertion of SeMet anti-PDCoV replication function. Meanwhile, HK2, a key rate-limiting enzyme of the glycolytic pathway, was able to control PDCoV replication in LLC-PK1 cells, suggesting a strategy for viruses to evade innate immunity using glucose metabolism pathways. Overall, based on the ability of selenomethionine to control PDCoV infection and transmission, we provide a molecular basis for the development of new therapeutic approaches.


Assuntos
COVID-19 , MicroRNAs , Doenças dos Suínos , Animais , Células LLC-PK1 , Selenometionina/farmacologia , Suínos
18.
Virus Res ; 322: 198954, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36198372

RESUMO

Porcine deltacoronavirus (PDCoV) and porcine epidemic diarrhoea virus (PEDV) are the main porcine enteric coronaviruses that cause severe diarrhoea in piglets, posing huge threat to the swine industry. Our previous study verified that the co-infection of PDCoV and PEDV is common in natural swine infections and obviously enhances the disease severity in piglets. However, the effects of co-infection of PDCoV and PEDV on intestinal microbial community are unknown. In current study, the microbial composition and diversity in the colon of piglets were analyzed. Our results showed that both of PDCoV and PEDV were mainly distributed in the small intestines and caused severe damage of ileum but not colon in the co-inoculated piglets. Furthermore, we observed that PDCoV and PEDV co-infection alters the gut microbiota composition at the phylum, family and genus levels. The abundance of Mitsuokella and Collinsella at genus level were significantly increased in PDCoV-PEDV co-infection piglets. Spearman's correlation analysis further suggested that there existed strong positive correlation between Mitsuokella and TNF-α, IL-6 and IL-8 secretion, these two factors may together aggravating the small intestine pathological lesions. These results proved there existed obvious correlation between the disease severity caused by PDCoV-PEDV co-infection and intestinal microbial community.


Assuntos
Coinfecção , Infecções por Coronavirus , Microbioma Gastrointestinal , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Animais , Suínos , Coinfecção/veterinária
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 267(Pt 2): 120456, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34653807

RESUMO

The consumption of food infected with food-borne pathogens has become a global public health problem. Therefore, it is monitor food-borne infections to avoid health and financial consequences. The rapid detection and differentiation of bacteria for biomedical and food safety applications continues to be a significant challenge. Herein, we present a label-free surface-enhanced Raman scattering approach for separating harmful bacteria from food. The method relies on the ascorbic acid reduction method to synthesize silver nanoparticles (AgNPs) and a polydimethylsiloxane (PDMS) multi-hole filter membrane chip (AgNPs@PDMS multi-hole filter membrane chip). Surface-enhanced Raman spectroscopy (SERS) was used, followed by multivariate statistical analysis to differentiate five important food-borne pathogens, including Staphylococcus aureus, Salmonella typhimurium, Listeria monocytogenes, Clostridium difficiles and Clostridium perfringens. The results demonstrated that compared to normal Raman signals, the intensity of the SERS signal was greatly enhanced with an analytical enhancement factor of 5.2 × 103. The spectral ranges of 400-1800 cm-1 were analyzed using principal component analysis (PCA) and stepwise linear discriminant analysis (SWLDA) were used to determine the optimal parameters for the discrimination of food-borne pathogens. The first three principal components (PC1, PC2, and PC3) accounted for 87.3% of the total variance in the spectra. The established SWLDA model had 100% accuracy and cross-validation accuracy, which accurately distinguished the SERS spectra of the five species. In conclusion, the SERS technology based on the AgNPs@PDMS multi-hole filter membrane chip was useful for the rapid identification of food-borne pathogens and can be employed for food quality management.


Assuntos
Nanopartículas Metálicas , Análise Espectral Raman , Dimetilpolisiloxanos , Análise Discriminante , Prata
20.
Front Immunol ; 13: 972499, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36081520

RESUMO

Porcine Deltacoronavirus (PDCoV), an enveloped positive-strand RNA virus that causes respiratory and gastrointestinal diseases, is widely spread worldwide, but there is no effective drug or vaccine against it. This study investigated the optimal Selenium Nano-Particles (SeNPs) addition concentration (2 - 10 µg/mL) and the mechanism of PDCoV effect on ST (Swine Testis) cell apoptosis, the antagonistic effect of SeNPs on PDCoV. The results indicated that 4 µg/mL SeNPs significantly decreased PDCoV replication on ST cells. SeNPs relieved PDCoV-induced mitochondrial division and antagonized PDCoV-induced apoptosis via decreasing Cyt C release and Caspase 9 and Caspase 3 activation. The above results provided an idea and experimental basis associated with anti-PDCoV drug development and clinical use.


Assuntos
Infecções por Coronavirus , Coronavirus , Selênio , Doenças dos Suínos , Animais , Apoptose , Coronavirus/fisiologia , Masculino , Dinâmica Mitocondrial , Suínos
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