60 results about "HCV Genotyping" patented technology

The present invention relates to inhibiting the activity of non-genotype 1 hepatitis C virus (HCV) NS3-NS4A protease activity. More particularly, the invention relates to inhibiting the activity of the protease from HCV genotype-2 or HCV genotype-3. The methods of the invention emply inhibitors that act by interfering with the life cycle of the HCV and are also useful as antiviral agents. The invention further relates to compositions comprising such compounds either for ex vivo use or for administration to a patient suffering from genotype-2 or genotype-3 HCV infection. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention.

The present inventors have developed a culture system for genotype 3a, which has a high prevalence worldwide. Since intergenotypic recombinant genomes exploiting the replication characteristics of JFH1 will be a valuable tool for the genotype specific study of the replaced genes and related therapeutics, the present inventors constructed a genotype 3a/2a (S52/JFH1) recombinant containing the structural genes (Core, E1, E2), p7 and NS2 of strain S52 and characterized it in Huh7.5 cells. S52/JFH1 and J6/JFH viruses passaged in cell culture had comparable growth kinetics and yielded similar peak HCV RNA titers and infectivity titers. Direct genome sequencing of cell culture derived S52/JFH1 viruses identified putative adaptive mutations in Core, E2, p7, NS3 and NS5A; clonal analysis revealed, that all genomes analyzed exhibited different combinations of these mutations. Finally, viruses resulting from transfection with RNA transcripts of five S52/JFH1 recombinant containing these combinations of putative adaptive mutations performed as efficiently as J6/JFH viruses in Huh7.5 15 cells and were all genetically stable after viral passage. In conclusion, the present inventors have developed a robust and genetically stable cell culture system for HCV genotype 3a.

The invention relates to the discovery of a novel RNA sequence at the 3′ terminal sequence of hepatitis C virus (HCV) genome RNA. Included in the invention are the 3′ sequence, its complement, and their use for nucleic-acid based diagnostics and for developing and evaluating novel anti-HCV therapies. This sequence element, which is conserved among HCV genotypes, is likely to be essential for viral replication, and required for construction of full-length HCV cDNA clones capable of yielding infectious RNA, progeny virus or replication-competent HCV replicons. Such functional clones are useful tools for evaluation of therapeutic approaches and as substrates for developing candidate attenuated or inactivated HCV derivatives for vaccination against HCV.

The invention relates to a DNA microarray chip, in particular to a hepatitis C virus (HCV) genotyping DNA microarray chip. A solid-phase carrier substrate is used, and an oligonucleotide probe is designed in view of different genotypes of HCV so as to prepare the DNA microarray chip; and when matched with a PCR primer and other components, the DNA microarray chip can quickly and accurately classify the types of the hepatitis C virus in a blood sample.

The present inventors developed hepatitis C virus 6a/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and the complete NS2 were replaced by the corresponding genes of the genotype 6a reference strain HK6a. Sequence analysis of recovered 6a/2a recombinants from 2 transfection experiments and subsequent reverse genetic studies revealed adaptive mutations in E1 and E2. Conclusion: The developed 6a/2a viruses provide a robust in vitro tool for research in HCV genotype 6, including vaccine studies and functional analyses.

Genotype 7a has been identified recently, thus not much is known about the biology of this new, major HCV genotype. The present inventors developed hepatitis C virus 7a/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and the complete NS2 were replaced by the corresponding genes of the genotype 7a strain QC69 and characterized them in Huh7.5 cells. Sequence analysis of 7a/JFH1 recombinants recovered after viral passage in Huh7.5 cells following 4 independent transfection experiments revealed adaptive mutations in Core, E2, NS2, NS5A and NS5B. In reverse genetic studies the importance of these mutations for improved growth kinetics was shown. Adapted 7a/JFH1 viruses showed growth kinetics, infectivity and RNA titers comparable to a previously developed 3a/JFH1 reference virus. Conclusion: The developed 7a/JFH1 viruses provide a robust in vitro tool for research in HCV genotype 7, including vaccine studies and functional analyses.

The present inventors developed 5a/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and all of or part of NS2 were replaced by the corresponding genes of the genotype 5a reference strain SA13. Compared to the J6/JFH control virus, after transfection of in vitro transcripts in Huh7.5 cells, production of infectious viruses was delayed. However, in subsequent viral passages efficient spread of infection and HCV RNA titers as high as for J6/JFH were obtained. Infectivity titers were at all time points analyzed comparable to J6/JFH control virus. Sequence analysis of recovered 5a/2a recombinants from 2 serial passages and subsequent reverse genetic studies revealed adaptive mutations in p7, NS2 and/or NS3. Infectivity of the 5a/2a viruses was CD81 and SR-BI dependant, and the recombinant viruses could be neutralized by chronic phase sera from patients infected with genotype 5a. Conclusion: The developed 5a/2a viruses provide a robust in vitro tool for research in HCV genotype 5, including vaccine studies and functional analyses of an increasingly important genotype in South Africa and Europe.

The invention relates to a kit for genotyping hepatitis C virus (HCV), which comprises HCVNS5B gene amplification primers, HCVNCR conserved region gene amplification primers, an HCVRNA extraction reagent, a negative control, a positive control, a cDNA (complementary deoxyribonucleic acid) synthetic reagent, a PCR (polymerase chain reaction) solution and a PCR sequencing reagent, wherein the sequence of the HCVNS5B gene forward primer is disclosed as SEQ ID NO.1, the sequence of the HCVNS5B gene reverse primer is disclosed as SEQ ID NO.2, the sequence of the HCVNCR conserved region gene forward primer is disclosed as SEQ ID NO.3, and the sequence of the HCVNCR conserved region gene forward primer is disclosed as SEQ ID NO.4. The kit provided by the invention has the advantages of high detection sensitivity and good specificity, and can be used for detecting all the reported HCV genotypes (subtypes) at high speed (within 12-14 hours).

The present invention includes methods of genotyping and phenotyping HCV. In one embodiment, the methods of the invention can be used to determine whether a HCV isolate is resistant to an antiviral drug. The invention also includes primers for amplifying a HCV NS3 region and kits.

The invention relates to a disease pathogen gene detecting technology and particularly relates to a hepatitis C virus (HCV) genotyping kit which can be used for auxiliary diagnosis for infection of types 1a, 1b, 2a, 2b, 3a, 3b and 6a of HCV happening in China. According to the invention, a nylon membrane carrier is adopted, an oligonucleotide probe is designed according to the different genotypes of the HCV, a gene chip is prepared, and then, a PCR (Polymerase Chain Reaction) primer and other components are matched, so that the HCV in a blood sample can be rapidly and accurately typed. The HCV genotyping kit provided by the invention has the characteristics of rapidness, sensitivity, accuracy, high flux, simplicity, convenience, high sensitivity and strong specificity, and is capable of detecting various target sequences in hybridization reaction once, convenient to take materials, free of special equipment and low in instrument investment.

The invention discloses a nucleotide sequence and a kit for detecting hepatitis C viruses (HCV), and belongs to the technical field of molecular diagnosis. By a primer and a probe for detecting the HCV, virus RNA of seven HCV genotypes can be specifically amplified and detected. By the kit for detecting the hepatitis C viruses, accurate copy numbers of various subtypes of the HCV can be detected quickly, sensitively and accurately. The nucleotide sequence and the kit have the advantages of simplicity and convenience in operation, high specificity, high sensitivity, low cost, high throughput and the like, can be applied to clinical quick hyper-sensitive detection of HCV virus RNA, and provide reference to clinical diagnosis and treatment of hepatitis C.

The invention provides oligonucleotides and a testing agent used for rapidly and sensitively detecting, identifying or distinguishing various genotypes and subtypes of hepatitis C viruses (HCVs). In one embodiment, the invention provides universal primers and probes corresponding to all the HCVs and the universal primers and probes can capture universal or common nucleic acids from the HCV ethnic groups. In one embodiment, the primers and the probes can capture the nucleic acids from rarely seen, unclassified or unknown HCV genotypes, subtypes or strains. In another embodiment, the invention provides probes capable of clearly detecting or identifying the HCV genotypes 1-6 or distinguishing the genotypes. In one embodiment, the invention provides primers and probes capable of clearly detecting or identifying the HCV subtypes 1a and 1b and the subtype 1a with NS3-K80 or NS3-Q80 polymorphism.

The present inventors developed hepatitis C virus 2b/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and the complete NS2 were replaced by the corresponding genes of the genotype 2b reference strain J8. Sequence analysis of recovered 2b/2a recombinants from 2 transfection experiments revealed that 2b/2a was genetically stable. Conclusion: The developed 2b/2a viruses provide a robust in vitro tool for research in HCV genotype 2b, including vaccine studies and functional analyses.

Compositions and methods are provided relating to human anti-HCV E2 monoclonal antibodies. The antibodies of the invention bind to a conserved region of HCV E2 protein, and neutralize HCV influenza virus across multiple HCV genotypes. Embodiments of the invention include isolated antibodies and derivatives and fragments thereof, pharmaceutical formulations comprising one or more of the human anti-HCV monoclonal antibodies; and cell lines that produce these monoclonal antibodies.

A method for the treatment of hepatitis C infection genotype 1, 2, 4, 5, or 6, but not genotype 3 is provided comprising administering an effective amount of a combination of Compound (I), Compound (II), and Compound (III), or independently optionally their pharmaceutically acceptable salt, solvate or hydrate, optionally in a solid fixed dose composition.