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BACKGROUNDS & AIMS: The hepatitis C virus NS3 protein is taken up by myeloid cells in a TLR2-independent manner and activates myeloid cells via TLR2. This study aimed to identify the endocytic receptor(s) involved in the uptake of NS3 by myeloid cells and its relation with TLR2. METHODS: Inhibitors and transfected cells were used to identify the nature of the NS3-binding receptors expressed by myeloid cells. The cooperation between scavenger receptors (SRs) and TLR2 in the NS3-mediated activation of myeloid cells was evaluated using inhibitors, cells from TLR2(-/-) mice, and confocal microscopy. The involvement of SRs in NS3 cross-presentation was evaluated in vitro using an NS3-specific human T-cell clone. RESULTS: We observed that SRs are the main binding structures for NS3 on myeloid cells and identified the SRs SRA-1 and SREC-I as endocytic receptors for NS3. Moreover, both SRs and TLR2 cooperate in NS3-induced myeloid cell activation. CONCLUSION: This study highlights a central role for SRs in NS3
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Mouse anti Hepatitis C NS-3 Antigen antibody, clone BGN/1244/3B5 recognizes the Hepatitis C virus non-structural protein 3 (NS3).
Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a remarkable protein as it clearly plays multiple roles in mediating viral replication, host-cell interactions and viral pathogenesis. However, on the impact of cell growth, there have been different study results. NS5ATP9, also known as KIAA0101, p15PAF, L5, and OEACT-1, was first identified as a proliferating cell nuclear antigen-binding protein. Earlier studies have shown that NS5ATP9 might play an important role in HCV infection. The aim of this study is to investigate the function of NS5ATP9 on hepatocellular carcinoma (HCC) cell lines proliferation under HCV NS5A expression. The results showed that overexpression of NS5ATP9 inhibited the proliferation of Bel7402 cells, whereas knockdown of NS5ATP9 by interfering RNA promoted the growth of HepG2 cells. Under HCV NS5A expression, RNA interference (RNAi) targeting of NS5ATP9 could reverse the inhibition of HepG2 cell proliferation, suggesting that NS5ATP9 might be an anti-proliferation gene
The hepatitis C virus (HCV) is a pandemic human pathogen posing a substantial health and economic burden in both developing and developed countries. Controlling the spread of HCV through behavioural prevention strategies has met with limited success and vaccine development remains slow. The development of antiviral therapeutic agents has also been challenging, primarily due to the lack of efficient cell culture and animal models for all HCV genotypes, as well as the large genetic diversity between HCV strains. On the other hand, the use of interferon-α-based treatments in combination with the guanosine analogue, ribavirin, achieved limited success, and widespread use of these therapies has been hampered by prevalent side effects. For more than a decade, the HCV RNA-dependent RNA polymerase (RdRp) has been targeted for antiviral development, and direct-acting antivirals (DAA) have been identified which bind to one of at least six RdRp inhibitor-binding sites, and are now becoming a mainstay of highly
TY - JOUR. T1 - Proteolytic processing and membrane association of putative nonstructural proteins of hepatitis C virus. AU - Hijikata, M.. AU - Mizushima, H.. AU - Tanji, Y.. AU - Komoda, Y.. AU - Hirowatari, Y.. AU - Akagi, T.. AU - Kato, N.. AU - Kimura, K.. AU - Shimotohno, K.. PY - 1993/11/30. Y1 - 1993/11/30. N2 - By using a plasmid-based transient protein expression system in cultured cells and an in vitro transcription/translation system, we analyzed the proteolytic processing of the putative nonstructural protein region of the precursor polyprotein from a Japanese type of hepatitis C virus. In addition to the previously reported viral proteins, p21 and p70, we identified products of 4 kDa (p4), 27 kDa (p27), 56 kDa (p56), 58 kDa (p58), and 66 kDa (p66). These products were produced in a viral serine proteinase (proteinase 2)-dependent manner from the region downstream of p70 in the precursor polyprotein and were arranged as NH2-p70-p4-p27-p58(p56)-p66-COOH as determined with ...
In this study, we investigated the requirements for NS5A phosphorylation. Taking advantage of the different phosphorylation patterns of NS5A observed with two cloned full-length genomes, a genetic analysis was performed. Our results show that a continuous NS3-5A sequence is required for NS5A hyperphosphorylation. Mutations at various positions in the NS3-4B region, not affecting polyprotein processing, can reduce or enhance this NS5A modification. Thus, structural integrity of each of these proteins, forming most likely a multisubunit protein complex, is essential for differential phosphorylation of NS5A.. Although phosphorylation of NS5A is a biochemical trait conserved among all HCV isolates analyzed so far, the conditions required for this modification appear to differ between various genotypes and even between different isolates of the same genotype. In case of the genotype 1a HCV-H isolate, the phosphorylation patterns of NS5A expressed on its own or in the context of an NS2-5B polyprotein ...
Adaptor Proteins, Signal Transducing; Animals; Apoptosis; Carrier Proteins; Cell Transformation, Neoplastic; Hepatitis C; Humans; Liver Neoplasms; Nuclear Proteins; Tumor Suppressor Proteins; Viral Nonstructural Proteins; inhibitors; Virus Replication; src Homology Domains. ...
NS1 tests detect the non-structural protein NS1 of dengue virus in the serum using synthetically labeled antibodies. NS1 is detectable during the acute phase of dengue virus infections. NS1 tests can be as sensitive as molecular tests during the first 0-7 days of symptoms. After day 7, NS1 tests are not recommended. A positive NS1 test result is indicative of a dengue infection but does not provide serotype information. Find detail information about laboratory diagnosis of dengue fever.. ...
Influenza C contributes to economic damage caused by working days lost through absence or inefficiency and may occasionally cause an acute respiratory illness in a paediatric setting. All Influenza C sequences from the NCBI Influenza Virus Resource were examined to determine the date of the most recent common ancestor (t-MRCA), the average nucleotide substitution rate, and the location of residues under positive selection, for each of the seven genome segments of this virus. The segment with the deepest phylogeny was found to be segment 4, encoding the haemagglutinin-esterase protein (HE) with mean t-MRCA at 1890 of the common era (AD), at a 95% highest posterior density (HPD) of 1857-1924 AD. Other genome segments have slightly more recent common ancestors, ranging from mean t-MRCAs of 1916 AD (HPD 1891-1937) for segment 7, encoding the two non-structural proteins (NS) to 1944 AD (HPD 1940-1948) for segment 2 encoding the type 1 basic polymerase (PB1). On the basis of the Bayesian analysis a ...
Analysis of the PDZ binding specificities of Influenza A virus NS1 proteins.: The Influenza A virus non-structural protein 1 (NS1) is a multifunctional virulenc
Hepatitis C Virus NS3 Genotype 2b, 0.1 mg. |span class=Body|HCV is a small 50nm, enveloped, single-stranded, positive sense RNAvirus in the family Flaviviridae.
Hepatitis C Virus NS5 Genotype 3, 0.1 mg. |span class=Body|HCV is a small 50nm, enveloped, single-stranded, positive sense RNAvirus in the family Flaviviridae.
Generic options for Hepatitis C Virus NS3/4A Protease Inhibitor pharmaceutical drugs, including patent status, patent expiration dates, and more.
Hepatitis C Virus NS4 Monoclonal Antibody from Invitrogen for Western Blot, Immunohistochemistry, Flow Cytometry, Immunoprecipitation and ELISA applications. This antibody reacts with Virus samples. Clone: 1G7. Supplied as 100 ug purified antibody (1 mg/ml) in PBS with 0.01% sodium azide; pH 7.2.
Resistance to Direct-Acting Antiviral Agents in Treatment of Hepatitis C Virus Infections. By Mostafa K. El Awady and Reham M. Dawood. Compounds targeting nonstructural (NS) proteins of hepatitis C virus (HCV) demonstrate clinical promise, suggesting that NS3/NS4a, NS5A, or NS5B inhibitors are potential components in direct-acting antiviral (DAA) combination therapies. In vitro studies revealed dramatic inhibition of viral replication or alteration in subcellular localization of NS proteins. DAAs bind either to catalytic sites (NS3 and NS5B) or to domain-1 of NS5A. Although ,90% of the patients clear HCV RNA from their sera, a significant portion of cirrhotic patients suffer from resistance or virological relapse. Mutations in specific residues (Q80K) in NS3 (M28, A30, L31, and Y93 in genotypes 1a and 1b or L28, L30, M31, and Y93 in genotype 4) in NS5A and A282T in NS5B are associated with resistance to DAA [resistance-associated variants (RAVs)]. Current knowledge on the NS functions, mode of ...
WNV Nonstructural protein 1 research reagents are researched and produced in house with premium quality at affordable price. Bulk in stock.
2WHO: Identification and Biological Evaluation of a Series of 1H-Benzo[De]Isoquinoline-1,3(2H)-Diones as Hepatitis C Virus Ns5B Polymerase Inhibitors
2WHO: Identification and Biological Evaluation of a Series of 1H-Benzo[De]Isoquinoline-1,3(2H)-Diones as Hepatitis C Virus Ns5B Polymerase Inhibitors
Purification and analysis of the replication complex. (A) Experimental scheme of the procedure of purification of replication complex. (B) Silver-stained SDS-
Hall, S.J.; van Dijk, A.A.; Huismans, H., 1989: Complete nucleotide sequence of gene segment 8 encoding non-structural protein NS2 of SA bluetongue virus serotype 10
The protective immunity conferred by a set of recombinant vaccinia viruses containing the entire coding sequence of dengue virus type 4 nonstructural glycoprotein NS1 plus various flanking sequences was evaluated by using a mouse encephalitis model. Mice immunized with recombinant vNS1-NS2a, which expresses authentic NS1, were solidly protected against intracerebral dengue virus challenge. However, mice immunized with recombinants vNS1-15%NS2a and vRSVG/NS1-15%NS2a, which express aberrant forms of NS1, were only partially protected (63 to 67% survival rate). Serologic analysis showed that mice immunized with vNS1-NS2a developed high titers of antibodies to NS1 as measured by radioimmunoprecipitation, enzyme-linked immunosorbent assay, and complement-mediated cytolytic assays. In addition, a pool of sera from these animals was protective in a passive transfer experiment. Lower titers of NS1-specific antibodies were detected in sera of animals immunized with vNS1-15%NS2a or vRSVG/NS1-15%NS2a by ...
TY - JOUR. T1 - Membrane topology and function of dengue virus NS2A protein. AU - Xie, Xuping. AU - Gayen, Shovanlal. AU - Kang, Cong Bao. AU - Yuan, Zhiming. AU - Shi, Pei Yong. PY - 2013/4/1. Y1 - 2013/4/1. N2 - Flavivirus nonstructural protein 2A (NS2A) is a component of the viral replication complex that functions in virion assembly and antagonizes the host immune response. Although flavivirus NS2A is known to associate with the endoplasmic reticulum (ER) membrane, the detailed topology of this protein has not been determined. Here we report the first topology model of flavivirus NS2A on the ER membrane. Using dengue virus (DENV) NS2A as a model, we show that (i) the N-terminal 68 amino acids are located in the ER lumen, with one segment (amino acids 30 to 52) that interacts with ER membrane without traversing the lipid bilayer; (ii) amino acids 69 to 209 form five transmembrane segments, each of which integrally spans the ER membrane; and (iii) the C-terminal tail (amino acids 210 to 218) ...
TY - JOUR. T1 - Proteomic analysis of endothelial cell autoantigens recognized by anti-dengue virus nonstructural protein 1 antibodies. AU - Cheng, Hsien Jen. AU - Lin, Chiou Feng. AU - Lei, Huan Yao. AU - Liu, Hsiao Sheng. AU - Yeh, Trai Ming. AU - Luo, Yueh Hsia. AU - Lin, Yee Shin. PY - 2009/1. Y1 - 2009/1. N2 - We previously showed the occurrence of autoimmune responses in dengue virus (DV) infection, which has potential implications for the pathogenesis of dengue hemorrhagic syndrome. In the present study, we have used a proteomic analysis to identify several candidate proteins on HMEC-1 endothelial cells recognized by anti-DV nonstructural protein 1 (NS1) antibodies. The target proteins, including ATP synthase β chain, protein disulfide isomerase, vimentin, and heat shock protein 60, co-localize with anti-NS1 binding sites on nonfixed HMEC-1 cells using immunohistochemical double staining and confocal microscopy. The cross-reactivity of anti-target protein antibodies with HMEC-1 cells was ...
Interferon alpha (IFN-α) is the key component of the therapy for hepatitis C virus (HCV) infection. IFN-α exerts anti-HCV activity by targeting certain signaling pathways. Using infectious HCV culture system in human hepatoma Huh7.5.1 cells, we analyzed functional relevance of extracellular signal-regulated kinase (ERK) pathway for IFN-α-mediated anti-HCV activity. IFN-α treatment resulted in activation of ERK pathway by increasing phosphorylation of c-Raf, MEK, and ERK1/2 in Huh7.5.1 cells, whereas HCV impaired such activation. IFN-α-dependent ERK1/2 phosphorylation was blocked by MEK inhibitor U0126. Pharmacological inhibition of ERK1/2 by U0126 or siRNA-mediated knockdown of ERK1/2 resulted in suppressive effects on HCV RNA levels and expression of HCV nonstructural protein 3 and envelope protein 2, establishing an important role for ERK pathway in HCV replication. Moreover, induction of a set of antiviral genes by IFN-α was enhanced in HCV-infected Huh7.5.1 cells due to the ERK1/2 knockdown,
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Influenza virus NS1 protein stimulates translation of the M1 protein.: The influenza virus NS1 protein was shown to stimulate translation of the M1 protein. M-C
Sigma-Aldrich offers abstracts and full-text articles by [Dorothee A Vogt, Grégory Camus, Eva Herker, Brian R Webster, Chia-Lin Tsou, Warner C Greene, Tien-Sze Benedict Yen, Melanie Ott].
Clinical Pharmacokinetics and Antiviral Activity of CC-31244, a Pan-genotypic, Potent Nonnucleoside NS5B Polymerase Inhibitor (NNI) for the Treatment of Hepatitis C ...
Hi! I plan to edit this article by providing an overview of what a viral protein is. The range of discovered viral proteins today is vast, and its very difficult to talk specifically about each and every one of them in a single article. I plan to talk about the four main types of viral proteins, namely viral structural proteins, viral nonstructural proteins, and viral regulatory and accessory proteins. Im certain that there may be other types of viral proteins that Im unaware of (due to limited general information about viral proteins available online) but Ill try my best to expand this article in a way that is helpful to the general audience. Im still working on the article, and I will be making edits to the main article page starting from April 5th.BiochemistrymafiaX (talk) 04:09, 13 April 2016 (UTC). ...
Recombinant DNA techniques were used to delete regions of a cDNA clone of the phosphoprotein NS gene of vesicular stomatitis virus. The complete NS gene and four mutant genes containing internal or terminal deletions were inserted into a modified pGem4 vector under the transcriptional control of the phage T7 promoter. Run-off transcripts were synthesized and translated in vitro to provide [35S]methionine-labeled complete NS or deletion mutant NS proteins. Immune coprecipitation assays involving these proteins were developed to map the regions of the NS protein responsible for binding to the structural viral nucleocapsid protein N and the catalytic RNA polymerase protein L. The data indicate the NS protein is a bivalent protein consisting of two discrete functional domains. Contrary to previous suggestions, the negatively charged amino-terminal half of NS protein binds to L protein, while the carboxyl-terminal half of NS protein binds to both soluble recombinant nucleocapsid protein N and viral ...
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Hepatitis C virus (HCV) is a positive-strand RNA virus grouped in the genus Hepacivirus within the family Flaviviridae. HCV is classified into at least 6 genotypes (gt), and its error-prone polymerase leads to more than 50 subtypes. The long open reading frame, which encodes the HCV polyprotein, is processed by host and viral proteases and gives rise to three structural proteins (the capsid protein core and envelope glycoproteins E1 and E2) and seven nonstructural (NS) proteins (p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B). NS2 and p7 are essential for virus assembly but not RNA replication, whereas NS3 to NS5B are involved in a membrane-associated RNA replicase complex (RC). The NS3 protein is composed of a serine protease and an RNA helicase/nucleoside triphosphatase (NTPase), NS4A serves as a cofactor for NS3 serine protease, NS5B is the RNA-dependent RNA polymerase, and NS5A is considered to play key roles in multiple steps of the HCV life cycle.NS5A inhibitors exhibit a rapid inhibition of ...
Human respiratory syncytial virus nonstructural protein (1C), nonstructural protein (1B), major nucleocapsid (N), phosphoprotein (P), protein (M), 1A (1A), G (G), protein (F) and envelope-associated protein (22K) gene, complete cds ...
HCV is currently one of the major health care problems in the world. In search of an alternative to the standard IFN-RBV treatment of HCV infection, we have discovered a series of potent inhibitors of the HCV NS5B RNA polymerase. A-837093 and A-848837 are two representative compounds from this series. While monotherapy often leads to resistance development (See posters 406, 432 talk 128), drug combinations have proven to deliver superior results in HIV therapy, and are almost certain to be most effective in treatment of HCV (Koev et al., 2006, Mo et al., 2005). In this study, we examined the short-term and long-term antiviral activity of Abbott HCV polymerase inhibitors A-837093 and A-848837 alone and in combination with IFN and the NS3 protease inhibitors BILN 2061 and SCH 503034. Our results indicate a great potential for successful combinations of our polymerase inhibitors with other drug classes ...
Nonstructural protein 5B (NS5B) is a viral protein found in the hepatitis C virus (HCV). It is an RNA polymerase, having the key function of replicating HCVs viral RNA by using the viral positive RNA strand as a template to catalyze the polymerization of ribonucleoside triphosphates (rNTP) during RNA replication. Several crystal structures of NS5B polymerase in several crystalline forms have been determined based on the same consensus sequence BK (HCV-BK, genotype 1). The structure can be represented by a right hand shape with fingers, palm, and thumb. The encircled active site, unique to NS5B, is contained within the palm structure of the protein. Recent studies on NS5B protein genotype 1b strain J4s (HC-J4) structure indicate a presence of an active site where possible control of nucleotide binding occurs and initiation of de-novo RNA synthesis. De-novo adds necessary primers for initiation of RNA replication. Several drugs either on the market or in various stages of research target NS5B as ...
Sigma-Aldrich offers abstracts and full-text articles by [Gregory Camus, Eva Herker, Ankit A Modi, Joel T Haas, Holly R Ramage, Robert V Farese, Melanie Ott].
DescriptionInfluenza A is responsible for tens of thousands of annual fatalities in the United States. The conventional medical strategy relies on prevention of infection using vaccines where are mildly effective at best and require yearly updates to reflect the expected prevalent strains, and anti-viral drugs for which there is significant clinical resistance. With this in mind, the non-structural protein 1 of influenza A (NS1A) is an appropriate target with high conservation and a multitude of anti-immune effects. It features an array of high surface area interactions which may be targetable using peptides. We are developing molecular design tools to reliably create short ...
Sensitivity of PR63cc to the combinatory treatment with asunaprevir and daclatasvir. Huh7.5.1 cells infected with PR63cc or JFH1 at an MOI of 0.05 for 3 days were treated with either asunaprevir, daclatasvir or in combination for another 3 days. 40 nM asunaprevir and 0.05 nM daclatasvir, approximately the EC50 concentration of the each inhibitor for JFH1, were used. The antiviral efficiency of each compound was evaluated by quantifying the intracellular HCV RNA by RT-qPCR. Data were expressed as the percentage of mock treatment control. The error bars were calculated from two independent experiments. ns, P > 0.05. *, P < 0.05 ...
Investigational Triple DAA Regimen of Daclatasvir, Asunaprevir and BMS-791325 Achieved SVR12 of 94% in Treatment-Naïve Patients with Genotype 1 Chroni
This trial is investigating the safety, tolerability and efficacy of asunaprevir plus daclatasvir in patients coinfected with HIV-HCV.
- Results of Phase 1 clinical studies support advancement to Phase 2 - InterMune, Inc. today announced that four abstracts from clinical and in-vitro studies of
THE BioTek is a leading large-scale manufacturer of antibodies, viral antigens, recombinant proteins, PCR Enzymes, and other reagents.
HCV-positive people whose HCV levels have not sufficiently responded to therapy are often referred to as null responders by researchers. Some of these ...
The neuroprotective effects of NS 521 were being investigated in Demmark with NeroSearch. However, development has been discontinued.
Аннотация: В статье описывается возможность применения масс-спектрометрии ультравысокого разрешения ионно-циклотронного резонанса в сочетании с «мягкими» методами ионизации для изучения качественного состава гетероатомных соединений нефти на молекулярном уровне. В образцах двух нефтей с различными свойствами идентифицировано 19 классов гетероатомных соединений, включая карбоновые кислоты, пиридиновые основания, пиррольные соединения, соединения с одним и двумя атомами серы в молекуле, а также гибридные соединения (SO, NS, O2S2, ONS и др.). ...
BACKGROUND: CD4+ T cell help is critical in maintaining antiviral immune responses and such help has been shown to be sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4+ T cell helper responses appear to be absent or short-lived, using functional assays. METHODOLOGY/PRINCIPAL FINDINGS: Here we used a novel HLA-DR1 tetramer containing a highly targeted CD4+ T cell epitope from the hepatitis C virus non-structural protein 4 to track number and phenotype of hepatitis C virus specific CD4+ T cells in a cohort of seven HLA-DR1 positive patients with acute hepatitis C in comparison to patients with chronic or resolved hepatitis C. We observed peptide-specific T cells in all seven patients with acute hepatitis C regardless of outcome at frequencies up to 0.65% of CD4+ T cells. Among patients who transiently controlled virus replication we observed loss of function, and/or physical deletion of tetramer+ CD4+ T cells before viral recrudescence. In some patients with