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Molecular Epidemiology of Plasmid-Mediated Types 1 and 3 Fimbriae Associated with Biofilm Formation in Multidrug Resistant Escherichia coli from Diseased Food Animals in Guangdong, China.

Types 1 and 3 fimbriae in Enterobacteriaceae play versatile roles in bacterial physiology including attachment, invasion, cell motility as w … 7 Klebsiella pneumoniae using archived WGS data, and shared high homology to those on plasmids of 8 replicon types and chromosomes from 6 Enterobacteriaceae species from various origins and countries. In contrast, fimACDH operons was present in most of Enterobacter cloacae (62.15%), and shared high homology to those with only a small group of plasmids and …

Antiviral Activity of Remdesivir and Obeldesivir Against SARS-CoV-2 Omicron Subvariants That Were Circulating from September 2023 Through June 2025.

With the ongoing emergence of SARS-CoV-2 variants, continued surveillance of antiviral susceptibility remains critical for detecting resista … 2 substitution, D284Y (detected in NB.1.8.1), was observed. Phenotypic analysis demonstrated that a replicon containing this substitution remained susceptible to both RDV and ODV. These findings are consistent with previous studies showing that RDV and ODV retain potent activity against previously identified Omicron variants, support the continued clinical …

Synthesis and Biological Evaluation of Modified Peptide Derivatives Targeting the SARS-CoV‑2 Nsp3 Macrodomain (Mac1) Replication Domain.

Modified peptide derivatives (D1-D15) containing hydrophobic (phenylalanine and tryptophan) and positively charged (histidine) amino acid re … wer than that of ADP-ribose. Subsequent bioactivity assays, performed using a cell-based SARS-CoV-2 replicon system, revealed that compound D15 displays the most potent inhibition of viral replication (IC50 = 22.2 μM (95% CI: 15.4-35.7 μM)), while compound D14 shows the second most potent inhibitory activity (IC50 = 61.2 μM (95% CI: 39.2-143.9 μM)). Consid …

Scutellaria barbata D. Don extracts alleviate SARS-CoV-2 induced acute lung injury by inhibiting virus replication and bi-directional immune modulation.

The emergence of SARS-CoV-2 variants and drug-resistant mutants emphasizes the urgent need to develop novel antiviral agents. In the present study, we examined the therapeutic effect of the Chinese medicinal herb, Scutellaria barbata D. Don (SBD), against SARS-CoV-2 infection both in vitro and in vivo. Using a viral replicon particle (VRP)-based mouse model of SARS-CoV-2 infection, our study revealed that SBD extracts can reduce viral load in mouse lungs and alleviate the viral induced pneumonia. In vitro antiviral determination further validated the direct acting antiviral efficacy of SBD ext…

A binary self-amplifying expression platform enabling lipid nanoparticle-free vaccines and nanomedicines.

Conventional mRNA vaccines played a crucial role in mitigating the COVID-19 pandemic but remain hampered by inherent instability, transient expression, limited payload capacity, and complex manufacturing, including their reliance on lipid nanoparticle (LNP) encapsulation. To address these challenges, this study describes the Gemini platform, an expression system with a bifunctional eukaryotic-prokaryotic promoter that can be deployed as either a self-amplifying RNA (saRNA) or as a self-amplifying DNA (saDNA) replicon, enabling robust amplification and expression of genetic cargo. Gemini elimin…

Masitinib Inhibits Hepatitis A Virus Replication.

The hepatitis A virus (HAV) infection causes acute hepatitis. HAV also induces acute liver failure or acute-on-chronic liver failure; however, no potent anti-HAV drugs are currently available in clinical situations. For anti-HAV drug screening, more convenient and useful models that mimic HAV replication are needed. In the present study, we established HuhT7-HAV/Luc cells, which are HuhT7 cells stably expressing the HAV HM175-18f genotype IB subgenomic replicon RNA harboring the firefly luciferase gene. This system was made by using a PiggyBac-based gene transfer system that introduces nonvira…

The role of capsid in the flaviviral life cycle and perspectives for vaccine development.

The arthropod-borne flaviviruses cause a series of diseases in humans and pose a significant threat to global public health. In this review, … o CPs can be used to rationally design safe and effective live-attenuated vaccines or noninfectious replicon vaccines and single-round infectious particles, the latter two representing promising approaches for innovative flaviviral vaccine development.

Methylene blue is a potent and broad-spectrum inhibitor against Zika virus in vitro and in vivo.

Many flaviviruses including the Dengue virus (DENV), Zika virus (ZIKV), West Nile virus, Yellow Fever virus, and Japanese encephalitis virus … confirmed that methylene blue works in both entry and post entry steps, reduces virus production in replicon cells and inhibited production of processed NS3 protein. Overall, we have shown that methylene blue is a potent antiviral for management of flavivirus infections, particularly for Zika virus. As an FDA-approved drug, methylene blue is well-tolerated …

Synthesis and evaluation of 2'-dihalo ribonucleotide prodrugs with activity against hepatitis C virus.

Hepatitis C virus (HCV) nucleoside inhibitors have been a key focus of nearly 2 decades of HCV drug research due to a high barrier to drug resistance and pan-genotypic activity profile provided by molecules in this drug class. Our investigations focused on several potent 2'-halogenated uridine-based HCV polymerase inhibitors, resulting in the discovery of novel 2'-deoxy-2'-dihalo-uridine analogs that are potent inhibitors in replicon assays for all genotypes. Further studies to improve in vivo performance of these nucleoside inhibitors identified aminoisobutyric acid ethyl ester (AIBEE) phosph…

A safe and reliable neutralization assay based on pseudovirus to measure neutralizing antibody titer against poliovirus.

With the promotion of inactivated poliomyelitis vaccine (IPV) and live attenuated oral poliomyelitis vaccine (OPV), the global reported case … type 1, 2, 3 attenuated strains by constructing poliovirus capsid expression vectors and poliovirus replicon then transfecting HEK293T cells and developed a pseudovirus-based neutralization assay (pNA) to determine neutralizing antibody titer which is more secure, time-saving and reliable than conventional neutralization assay (cNA). By using anti-poliovir …

Characterization of an rmtB-carrying IncI1 ST136 plasmid in avian Escherichia coli isolates from chickens.

The rmtB gene, one of the 16S rRNA methylase genes whose products confer high-level resistance to aminoglycosides, is most prevalent among Enterobacteriaceae strains. In this study, eight non-duplicate rmtB-carrying avian Escherichia coli strains from a farm in China were isolated and characterized, and further examined by phylogenetic grouping, conjugation experiments and PCR-based replicon typing. In addition, the genetic environment of rmtB was investigated by cloning and sequencing. Six rmtB-carrying E. coli were identified as phylogroup A, sequence type (ST) 156 (A-ST156), with two assign…

Antiviral activity of selected flavonoids against Chikungunya virus.

This study focuses on the antiviral activity of selected flavonoids against the Chikungunya virus (CHIKV), a mosquito-transmitted virus that can cause incapacitating arthritis in infected individuals. Based on the results of screening on Vero cells, the tested compounds were evaluated further with various assays, including cytotoxicity assay, virus yield assay by quantitative reverse transcription polymerase chain reaction (qRT-PCR), virus RNA replication assay with a CHIKV replicon cell line, Western blotting, and quantitative immunofluorescence assay. Baicalein, fisetin, and quercetagetin di…

Suppressive effect of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) on hepatitis C virus replication.

The histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) has a clinical promise for treatment of cancer including hepatocellular carcinoma (HCC). To investigate effect of SAHA on hepatitis C virus (HCV) replication, we treated the HCV replicon cell OR6 with SAHA. HCV replication was significantly inhibited by SAHA at concentrations below 1 μM with no cellular toxicity. Another HDAC inhibitor, tricostatin A, also showed reduction of HCV replication. The microarray analysis and quantitative RT-PCR demonstrated up-regulation of osteopontin (OPN) and down-regulation of apoli…

Molecular characterization of hepatitis E virus ORF1 gene supports a papain-like cysteine protease (PCP)-domain activity.

Hepatitis E Virus (HEV) ORF1 encodes the nonstructural polyprotein wherein a role of PCP-domain in ORF1 proteolysis and/or RNA replication still remains contested. A series of ORF1 mutants of HEV-SAR55 replicon were constructed and tested for viability in S10-3 cells. Six of PCP-'cysteine' (C457A, C459A, C471A, C472A, C481A and C483A) and three 'histidine' (H443L, H497L and H590L) mutants were lethal. Further, a highly conserved 'glycine-triad' (G815-G816-G817) in downstream X-domain, homologous to rubella virus protease-substrate (G1299-G1300-G1301) was identified where two of X-mutants (G816…

Ribavirin inhibits in vitro hepatitis E virus replication through depletion of cellular GTP pools and is moderately synergistic with alpha interferon.

Hepatitis E virus (HEV) is a common cause of acute hepatitis that results in high mortality in pregnant women and may establish chronic infections in immunocompromised patients. We demonstrate for the first time that alpha interferon (IFN-α) and ribavirin inhibit in vitro HEV replication in both a subgenomic replicon and an infectious culture system based on a genotype 3 strain. IFN-α showed a moderate but significant synergism with ribavirin. These findings corroborate the reported clinical effectiveness of both drugs. In addition, the antiviral activity of ribavirin against wild-type genotyp…

Блок DEAD RNA Heliace DDX5 действует в качестве позитивного регулятора японского энцефалитного репликации путем подключения к вирусу 3' UTR.

Японский энцефалитный вирус (JEV), являющийся одной из причин эпидемического энцефалита, принадлежит семье Флавивиридае. В этом исследовании мы продемонстрировали, что клеточный блок DEAD-box RNA Heliace DDX5 играет важную роль в воспроизведении JEV. Отключение DDX5 позволило сократить тиражирование JEV, а перевыражение DDX5 мутантов, не имеющих активности велек, также сократило тиражирование JEV, что говорит о том, что деятельность ветряной системы имеет важное значение для воспроизведения JEV. DDX5 не повлиял на сборку и высвобождение вирусов. Эксперименты GST-pulldown и совместного иммунно-

Совпадение в аннотации оригинала
Japanese encephalitis virus (JEV), one of the causes for epidemic encephalitis, belongs to the family of Flaviviridae. In this study, we dem … untranslated region (UTR). Finally, we confirmed the role of DDX5 in JEV RNA replication using JEV-replicon system. In conclusion, we identified DDX5 as a positive regulator for JEV replication.

Recovery of a chemically synthesized Japanese encephalitis virus reveals two critical adaptive mutations in NS2B and NS4A.

A full-length genome infectious clone is a powerful tool for functional assays in virology. In this study, using a chemical synthesized comp … ing to viruses with a large-plaque phenotype. Mutagenesis analysis, using a genome-length RNA and a replicon of JEV, demonstrated that the adaptive mutations restored replication to different degrees, and the restoration efficiencies were in the order: NS2B-T102M<NS4A-R79K<NS2B-T102M+NS4A-R79K. An in vivo virulence assay in mice showed that the recombinant …

Epidemiology of Escherichia coli, Klebsiella species, and Proteus mirabilis strains producing extended-spectrum β-lactamases from clinical samples in the Kinki Region of Japan.

In the present study, nonduplicate, clinical isolates of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli, Klebsiella spp, an … ST131 producing CTX-M-15, which is spreading worldwide, was first detected in 2007. The most common replicon type of E coli was the IncF type, particularly FIB, detected in 466 strains (69.7%). Of the K pneumoniae strains, 47 (55.3%) were of the IncN type; 77 P mirabilis strains (96.3%) were of the IncT type. In the future, the surveillance of various resi …

2,3-Dihydro-1,2-Diphenyl-substituted 4H-Pyridinone derivatives as new anti Flaviviridae inhibitors.

With the aim of identifying novel lead compounds active against emergent human infectious diseases, a series of 2,3-dihydro-4H-pyridinone de … these, compound 6a displayed great inhibitory activity against Hepaciviruses (hepatitis C virus) in replicon assay [CC(50) > 100 μm; EC(50) (1b) = 4 μm]. In vitro inhibitory activity against the HCV RNA-dependent RNA polymerase (NS5B) of title compounds is discussed. The antiviral screening of viral strains indicated that compound 6a can be selected as pro …

Prevalence of plasmid-mediated AmpC beta-lactamases among Enterobacteriaceae in Algiers hospitals.

The aim of this study was to investigate the prevalence and diversity of plasmid-mediated AmpC cephalosporinases (PAcBLs) in clinical isolat … ts were sequenced by the Sanger method. Plasmid incompatibility grouping was conducted by PCR-based replicon typing. The prevalence of PAcBLs was 2.18% (11/505), comprising 8 CMY-2 and 3 DHA-1 enzymes. CTX-M-15 was co-produced with CMY-2 in three isolates and with DHA-1 in one isolate; the two remaining DHA-1-producers co-expressed SHV-12 ESBL. This is the …