66 results about "Hepatitis b viral" patented technology

The invention relates to the field of immunology, and particularly discloses a hepatitis B virus specific TCR combination and application, the hepatitis B virus specific TCR combination is used for recognizing HBV antigen epitopes, the hepatitis B virus specific TCR combination comprises a plurality of separated TCRs, the plurality of separated TCRs form two TCR groups, and the two TCR groups comprise a first TCR group and a second TCR group; wherein the first TCR group specifically recognizes a first antigen epitope, and the amino acid sequence of the first antigen epitope is as shown in SEQ ID NO: 1; the first TCR group specifically recognizes a first antigen epitope, the second TCR group specifically recognizes a second antigen epitope, the amino acid sequence of the second antigen epitope is shown as SEQ ID NO: 2, the second antigen epitope respectively and correspondingly recognizes different antigen epitopes, the hepatitis B virus specific TCR and the epitope thereof are screened out, and an important means can be provided for treatment of TCR-T immune cells infected by hepatitis B virus.

The invention relates to the technical field of biological medicines, in particular to a vaccine for treating or preventing hepatitis B virus infection. The vaccine comprises a hepatitis B surface antigen and a composite adjuvant, wherein the composite adjuvant is prepared from CpG oligodeoxynucleotide and saponin QS-21, and the composite adjuvant is prepared from CpG oligodeoxynucleotide and saponin QS-21; the nucleotide sequence of the CpG oligodeoxynucleotide is as shown in SEQ ID NO. 1. According to the vaccine provided by the invention, an HBsAg antibody can be generated in a normal mouse body, and HBV in an HBV-carrier mouse can be effectively eliminated, so that the vaccine has the effect of treating or preventing hepatitis B virus infection. According to the vaccine provided by the invention, two adjuvants, namely CpG oligodeoxynucleotide and saponin QS-21, are adopted, so that the vaccine can be used for synergistically activating an immune effect, enhancing the activation of B cells and permanently transforming into plasma cells, and meanwhile, the vaccine can be used for resisting immune tolerance of T cells, realizing the removal of hepatitis B viruses and realizing functional cure of clinical hepatitis B treatment.

The invention belongs to the technical field of biological medicines, and particularly relates to an mRNA vaccine for preventing or treating hepatitis B virus infection and application of the mRNA vaccine. The mRNA vaccine comprises mRNA for coding hepatitis B virus surface antigen or / and hepatitis B virus core associated antigen or / and hepatitis B virus front surface antigen 1 fusion IgG Fc segment protein, and the mRNA is wrapped by lipid nanoparticles to form a delivery system to be prepared into the mRNA vaccine. The vaccine preparation can specifically enhance humoral immune response and cellular immune response aiming at hepatitis B virus surface antigen or / and hepatitis B virus core related antigen or / and hepatitis B virus front surface antigen, and can be used for preventing and treating hepatitis B. All the components in the vaccine preparation can be widely obtained, the vaccine cost is effectively reduced, the vaccine yield is increased, and therefore the vaccine preparation has good practical application value.

2'-Fluoro-6'-methylene-carbocyclic adenosine (FMCA, 21) and its phosphoramidate prodrug (FMCAP, 31) have demonstrated potential anti-HBV activity against both adefovir- resistant as well as lamivudine-resistant double (rtL180M / rtM204V) mutant hepatitis B virus (HBV). In addition, in vitro, these molecules have reinstated a significant activity against lamivudine / entecavir triple mutants (L180M+S202G+M204V). This invention is directed to compounds, pharmaceuticals and methods of treating HBV infections, especially including infections caused by resistant and multiple resistant HBV. Pursuant to the present invention, a complete structure-activity relationship (SAR) of 2'-fluoro-6'-methylene-carbocyclic derived nucleos(t)ides has been evaluated and that analysis is presented herein. Pursuant to the present invention, the synthesis and antiviral evaluation of purine and pyrimidine-derived nucleosides have been reported against wild-type and various HBV mutants. Guanosine analog (FMCG, 25) demonstrated an EC50 value of 0.217μM and cytosine analog (FMCC, 41) expressed a potent EC50 value of 0.0025 μM compared to entecavir (EC50 = 0.0029) against wild-type HBV. Additionally, FMCC (41) maintains its antiviral potency against various HBV mutants. Furthermore, chiral pure FMCAP Sp (34) isomer demonstrated an EC50 value of 1.3 nM and was more potent against several HBV mutants than entecavir.

The application discloses a low-cost hepatitis B (HBV) virus nucleic acid rapid detection method based on a functionally modified paper base, and can realize rapid detection of HBV virus nucleic acid.The method comprises the following steps: (1) pre-amplifying HBV virus nucleic acid to obtain Texas red-labeled nucleic acid; (2) capturing and enriching the Texas red-labeled nucleic acid by using a functionally modified paper base; and (3) performing signal detection.The functionally modified paper base is modified with a fusion protein containing a TR512 polypeptide.The protein functionally modified paper base is simple in preparation, fast in nucleic acid detection time and low in detection cost.

The present application relates to the technical field of knowledge graph, in particular to a multi-task hepatitis B drug screening method and system based on knowledge graph assistance, comprising the following steps: based on hepatitis B virus genotype sequence data recorded over time, patient drug use records and drug sensitivity. In the present application, multi-dimensional dynamic time series data such as virus genotype sequence data, patient drug use records and drug sensitivity are integrated, the interaction events between entities are marked by time stamp, the dynamic characteristics such as virus variation track and drug efficacy change are embedded in the graph node attributes, so that the knowledge representation can reflect the time dependence in the real scene. Based on biological pathway annotation information and protein interaction data, the hyperedge connection multi-entity set is defined, the limitation of traditional knowledge graph which only supports binary relationship is expanded, the drug combination and multi-target synergistic mechanism are explicitly modeled, and the misjudgment of combination effect caused by the simplification of interaction relationship is avoided.

Provided are a combination comprising a drug for treating hepatitis B and an antiviral agent, and a use thereof. The drug for treating hepatitis B comprises a nucleic acid or nucleic acid combination (e.g., an mRNA combination) encoding an antigen of hepatitis B virus. The combined use of the drug for treating hepatitis B and the antiviral agent can significantly reduce the number of liver HBV Core positive cells in an infected subject, greatly improve the HBV-specific T cell response level in the subject, and shows no obvious rebound of HBsAg after drug withdrawal.

The present disclosure relates to a ribavirin derivative-embedded double-stranded siRNA analogue, a conjugate comprising the same, and salts and uses thereof. The double-stranded siRNA analogue, the conjugate comprising the same, and the salts thereof of the present disclosure can effectively inhibit multiple viral indicators such as hepatitis B virus DNA, pgRNA, S antigen, E antigen, etc., and provide an effective and feasible method for the treatment of hepatitis B.

This invention relates to compositions, methods, strategies, and treatment modalities related to the epigenetic modification of hepatitis B virus (HBV) genes.

The invention discloses a traditional Chinese medicine composition for treating fatty liver and reducing hepatitis B virus load. The traditional Chinese medicine composition is prepared from the following raw material medicines: prepared rehmannia root, rhizoma polygonati (processed), radix asparagi, schisandra chinensis, hawthorn leaf, glossy privet fruit, oriental wormwood, radix curcumae, illicium verum and salvia miltiorrhiza. According to the technology of the invention, liver treatment is a preparation based on compatibility of traditional Chinese medicine syndrome differentiation in which liver, spleen and kidney are treated at the same time, fat in the liver can be effectively removed, damage of hepatitis B virus to the liver can be reduced, hepatitis B virus reproduction can be effectively inhibited, the load of hepatitis B virus can be reduced, and multiple curative effects of liver treatment, liver nourishing and liver protection can be realized; the traditional Chinese medicine composition is superior to other treatment medicines and treatment technologies for fatty liver in modern medicine. The method can be widely applied to the fields of medicines, functional foods, health-preserving and health-care products, common foods and beverages and the like.

The present invention relates to a dual-target double-stranded RNA for treating hepatitis B, and a pharmaceutical composition. The dual-target double-stranded RNA comprises a first double-stranded RNA and a second double-stranded RNA, wherein one of the first double-stranded RNA and the second double-stranded RNA targets the hepatitis B virus (HBV) life cycle, and the other targets a host immune target PD-L1. The double-stranded RNA can simultaneously target the dual targets of HBV and host immune PD-L1, which can inhibit HBV replication while activating human immunity, and is therefore expected to bring about a clinical functional cure.

The invention discloses a bipyrimidine heterocyclic compound and a preparation method and application thereof, the bipyrimidine heterocyclic compound has a structure as shown in a formula (I), and the invention also provides a pharmaceutical composition containing the compound or a stereoisomer, a medicinal salt, a hydrate, a solvate or a crystal thereof. The invention also discloses application of the compounds in preparation of drugs for treating hepatitis B virus infection, and particularly the compounds can be used as PAPD5 / 7 enzyme inhibitors and hepatitis B RNA non-stabilizers for treating hepatitis B viruses. The compound provided by the invention has the characteristics that the concentration of hepatitis B surface antigen and hepatitis B DNA and RNA can be remarkably reduced, and the probability of functional healing of hepatitis B can be remarkably improved by clinically combining with nucleoside drugs, oligonucleotide drugs / PD-L1 compounds and the like.

Provided herein are non-naturally occurring variants of the hepatitis B virus (HBV) Core protein, the HBV polymerase N-terminal domain, and the HBV polymerase C-terminal domain, as well as immunogenic fragments thereof. Fusion proteins comprising the HBV variants fused to a herpes simplex virus (HSV) glycoprotein (gD) sequence, as well as methods of using the fusion proteins, are also provided.

The utility model relates to a convenient-to-titrate hepatitis B virus five-item detection kit, which solves the technical problem that the dropping position is easy to be inaccurate when the existing detection kit detects dropping buffer solution, and comprises a sample adding hole, slots arranged on the side wall of a detection card body are symmetrically arranged on two sides of the sample adding hole, and the slots are arranged on the side wall of the detection card body. The detection card body is provided with a plurality of slots, the slots are detachably matched with arched limiting plates in a sliding manner, the inner sides of the lower ends of the limiting plates are fixedly provided with inserting blocks matched with the slots, the limiting plates are provided with limiting holes corresponding to the sample adding holes, and integrated disposable buffer solution devices are inserted into the limiting holes. After the limiting plate is inserted into the detection card body, a limiting foundation for subsequently dropwise adding a buffer solution can be fixed, and after a buffer solution device is arranged, the accuracy of dropwise adding the buffer solution can be improved, the buffer solution can be accurately dropwise added, meanwhile, the waste of the buffer solution is avoided, the buffer solution is saved, and only a small amount of buffer solution needs to be prepared.

This invention belongs to the field of affinity membrane and bioseparation technology, and provides a cellulose-based affinity membrane for hepatitis B virus (HBV), its preparation method, and its application. The affinity membrane consists of a base membrane and an affinity ligand immobilized on the base membrane. The base membrane is a carboxylated cellulose filter membrane or a carboxylated modified cellulose filter membrane. The affinity ligand is a biomolecule that specifically recognizes HBV surface antigen. The carboxyl groups of the base membrane and the amino groups of the affinity ligand are linked by amide bonds. Unreacted carboxyl groups on the base membrane are blocked by a blocking reagent. The carboxyl content of the base membrane is 400-1000 μmol / g, the pore size is 400-1000 nm, and the porosity is 30%-60%. The application refers to the use of the above-mentioned affinity membrane in the specific clearance of HBV from HBV-positive plasma. This invention can achieve efficient and specific clearance of HBV from plasma, maximally preserving the activity and function of normal plasma components, and improving the feasibility of industrial application.

The invention discloses a screening method of hepatitis B virus antigen epitope peptides, computer equipment and a storage medium, and the method comprises the following steps: generating an initial screening library based on all proteome sequences of hepatitis B viruses, the initial screening library comprising a plurality of antigen epitope peptides to be screened; an antigen epitope peptide-MHC compound corresponding to each antigen epitope peptide is constructed; based on the antigen epitope peptide-MHC compound, a conformational trajectory of the antigen epitope peptide-MHC compound is obtained through molecular dynamics simulation; calculating the binding free energy of each antigen epitope peptide and the MHC based on the conformation trajectory, and sorting the plurality of antigen epitope peptides based on the binding free energy to obtain a first sorting set; based on the antigen epitope peptide-MHC compound, sorting the plurality of antigen epitope peptides by using a machine learning model to obtain a second sorting set; and screening the plurality of to-be-screened antigen epitope peptides based on the first sorting set and the second sorting set to obtain the screened antigen epitope peptides.

The application discloses a monoclonal antibody against hepatitis B virus e antigen and a preparation method and application thereof, and relates to the field of hepatitis B antigen detection. Specifically, the antibody provided by the application has HCDR1-3 as shown in SEQ ID NO: 1, 2 and 3 respectively, and LCDR1-3 as shown in SEQ ID NO: 4, 5 and 6 respectively. The provided antibody can specifically recognize human hepatitis B e antigen. The positive coincidence rate, the negative coincidence rate and the total coincidence rate of a detection reagent constructed using the antibody and the Abbott control reagent are all 100%. Compared with an existing antibody 3A3, the stability and the repeatability of detection are significantly improved, and the early detection rate of the reagent kit has important value.

The present disclosure is directed to novel compounds, salts thereof, compositions, and methods of using as well as synthesizing. The present disclosure is directed, at least in part, to compounds for the treatment of Hepatitis B (HBV) infection and compositions prepared therefrom. Methods of making and using the compounds for the treatment of Hepatitis B (HBV) infection are also provided.

Provided in the present application are a glycosylated fusion protein, a nucleic acid molecule, an expression vector, a host cell and the use thereof. A first aspect of the present application provides the glycosylated fusion protein, comprising a murine Fc variant and a hepatitis B virus antigen, wherein the murine Fc variant is obtained by performing amino acid mutation and non-mammalian glycosylation modification on a murine Fc fragment, the murine Fc variant comprises at least one of alanine at position 223, alanine at position 228, alanine at position 230, leucine at position 330, and glutamic acid at position 332, the glycosylation modification does not comprise sialic acid modification, and the positions are numbered according to the EU numbering system. The fusion protein can bind to DC cells and activate DC cells, and thus promote the proliferation and activation of specific T cells.

Provided are a pharmaceutically acceptable salt, a crystal form and a preparation method of a TLR7 / 8 agonist compound of formula I, a pharmaceutical composition containing the pharmaceutically acceptable salt, and a medical use of the pharmaceutically acceptable salt, which can be used for preparing drugs for preventing or treating Toll-like receptor 7 / 8 (TLR7 / 8) related diseases, such as a new therapeutic agent for human immunodeficiency virus (HIV) infection, hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection and cancer.

The present application relates to an immune stimulator and composition and its application and the preparation method of the composition, which can inactivate and eliminate the cells infected with hepatitis B virus on the basis of maintaining the original preventive vaccine hepatitis B virus specific antibody in animals and human bodies, has the dual effects of prevention and treatment; it has stronger immune activation effect than the original HBsAg antigen, which is reflected in the strengthened induction of immune cells, higher antibody production effect, especially the high level of Th1 type immune production marked by gamma-interferon and IgG2a antibody, which has significant innovation and practicability for eliminating hepatitis B virus.

The invention belongs to the field of biological medicines, and relates to a pharmaceutical composition and application thereof in preparation of medicines for preventing and treating hepatitis B virus. Comprising a nucleic acid drug and a carrier for loading the nucleic acid drug, the carrier can specifically target liver Kupffer cells, the nucleic acid drug is mRNA, and a gene sequence for coding the mRNA comprises nucleotide sequences shown as SEQ ID NO: 1 and SEQ ID NO: 2. The pharmaceutical composition provided by the invention can specifically activate Notch signal channels of Kupffer cells, and can play a role in treating and preventing hepatitis B; meanwhile, the anti-HBV effect of the pharmaceutical composition depends on the participation of Kupffer cells, and the pharmaceutical composition becomes a potential novel strategy for clinical treatment of chronic hepatitis B.

This invention relates to a fusion antigen mRNA molecule, which encodes a protein comprising at least two of the following: hepatitis B surface antigen protein sHBsAg, hepatitis B core antigen protein Core, hepatitis B X antigen protein HBxAg, and hepatitis B preS1 antigen protein PreS1, preferably comprising hepatitis B surface antigen protein sHBsAg, hepatitis B core antigen protein, and hepatitis B PreS1 antigen protein, denoted as sHBsAg-Core-PreS1, and its amino acid sequence is shown in SEQ ID No. 17; the above-mentioned fusion antigen mRNA molecule can be prepared into an mRNA-LNP vaccine composition and used to treat chronic hepatitis B virus infection. The preferred sHBsAg-Core-PreS1 mRNA-LNP of this invention can normally express and present each encoded target antigen in vivo, and achieve cross-presentation, cross-activation and enhanced expression, inducing target antigen-specific humoral and cellular immune responses. It can also effectively overcome immune tolerance in a mouse model of chronic hepatitis B, and has excellent antiviral and immunotherapeutic effects. Compared with existing related therapeutic HBV mRNA-LNP vaccines, it effectively improves the immune tolerance breakthrough threshold, providing a candidate vaccine and a new immunotherapy strategy for the immunotherapy of patients with chronic HBV infection.

The invention discloses a molecular imprinting colorimetric sensor for detecting hepatitis B virus as well as a preparation method and application of the molecular imprinting colorimetric sensor. The sensor takes an aminated zeolite imidazate framework material (ZIF-8-NH2) with peroxidase-like activity as a catalytic core, after surface double-bond functionalization, a molecularly imprinted polymer (MIPs) layer is constructed on the surface through a free radical polymerization reaction by taking the aminated zeolite imidazate framework material as a carrier and taking HBV as a template molecule. According to the sensor, after HBV is specifically recognized and captured through MIPs, the catalytic efficiency of ZIF-8 on hydrogen peroxide is changed, then the generation amount of hydroxyl radicals is regulated and controlled, and finally visual and quantitative detection of HBV is achieved through the color fading reaction of the hydroxyl radicals and chromogenic dye crystal violet. The sensor prepared by the invention has the advantages of high sensitivity, strong specificity, low cost, simplicity and convenience in operation, rapidness in detection and the like, and can be used for rapid screening and on-site instant detection of hepatitis B viruses.

A composition for treating chronic hepatitis B infection, comprising mRNA encoding a hepatitis B viral antigen, the mRNA being encapsulated in a lipid nanoparticle (LNP).

The application discloses a recombinant virus-like nanoparticle for immunotherapy of gastric cancer and application thereof. The recombinant virus-like nanoparticle is a chimeric recombinant virus-like nanoparticle formed by self-assembly of a fusion protein HBC-CLDN18.2 of a hepatitis B virus core protein and CLDN18.2 tight junction protein. The application uses genetic engineering technology to truncate the C-terminal end of a natural hepatitis B virus core antigen, and mutate cysteine residues at positions 48 and 107 into serine, so that the hepatitis B virus core antigen can self-assemble into a virus-like nanoparticle with strong stability. The virus-like nanoparticle is used as a carrier, a B cell epitope peptide (tight junction protein CLDN18.2) of a gastric cancer tumor-related antigen is inserted into an immunodominant site of the carrier, so that the humoral immune response against gastric cancer is enhanced. Two T cell epitope peptides of the heterologous hepatitis B virus core antigen are used to replace T cell epitope peptides on the carrier, so that the cellular immune response against gastric cancer is enhanced, and strong antitumor effect and immune memory effect are shown.

The present application relates to a kind of based on magnetic covalent organic framework material construction biological sensor method for detecting hepatitis B virus, the method includes Au@ZnFe2O4@COF Nanocomposite and intermediate product material: ZnFe2O4@COF.The outstanding creativity of the present application: 1.firstly using magnetic adsorption biological sensor detects HBV.2.design capture probe, signal probe and can specifically recognize the characteristic of hepatitis B virus DNA instead of using antibody to capture hepatitis B virus and utilize CuO laccase activity determination virus concentration sandwich type photochemical immunosensor.

The application discloses a hepatitis B surface antigen specific B cell receptor gene knock-in mouse model, and establishes a hepatitis B virus surface antigen (HBsAg) specific B cell receptor (BCR) gene knock-in mouse model, wherein 70-90% of B cells of the mouse can specifically recognize HBsAg, and differentiate into germinal center B cells and plasma cells. Therefore, the model can be used for basic research on hepatitis B antiviral humoral immune response and tolerance mechanism, and can also be used for application research on development of drugs and vaccines for breaking HBsAg immune tolerance. In summary, the establishment of the model lays a solid foundation for development of a functional cure immune means for hepatitis B.

The application discloses a primer probe combination for detecting hepatitis B virus, a detection product and application thereof, and relates to the technical field of hepatitis B virus detection. The primer probe combination comprises a forward primer HBV-FP, a reverse primer HBV-RP and a detection probe HBV-Probe. The nucleotide sequence of the forward primer HBV-FP is shown as SEQ ID NO. 1, the nucleotide sequence of the reverse primer HBV-RP is shown as SEQ ID NO. 2, and the nucleotide sequence of the detection probe HBV-Probe is shown as SEQ ID NO. 3. The 5' end of the detection probe HBV-Probe is coupled with a first fluorescent group, and the 3' end is connected with a quenching group. The detection system, the detection product and the detection method provided by the primer probe combination have good specificity, strong specificity, good linearity, good repeatability, high sensitivity and wide application prospect.

The invention discloses an application of host factors DDOST and SEC61A in regulation and control of hepatitis B virus antigen expression and HBV replication. A series of novel host factors for regulating and controlling HBsAg expression are identified, and by screening the host factors, DDOST and SEC61A1 show a strong inhibition effect on hepatitis B virus surface antigens in cell and mouse models, and are expected to be used for developing novel therapeutic drugs and therapeutic strategies for inhibiting the hepatitis B virus surface antigens.