16008results about "Antivirals" patented technology

Provided are compounds of Formula I:nucleosides, nucleoside phosphates and prodrugs thereof, wherein R6 is CN, ethenyl, 2-haloethen-1-yl, or (C2-C8)-alkyn-1-yl. The compounds, compositions, and methods provided are useful for the treatment of Flaviviridae virus infections.

The invention provides an artificial nucleic acid molecule which is used for improving the expression quantity of target amino acid, polypeptide or protein. The artificial nucleic acid molecule at least comprises a target 5'untranslated region (UTR), a target coding region (CDS) and a target 3 'untranslated region (UTR). Wherein the sequence of the target 5 'UTR is one of the following sequences: 5' UTR of a high-expression gene and a 5 'UTR variant of the high-expression gene. The sequence of the target 3 'UTR is one of the following sequences: 3' UTR of a high-expression gene and a 3 'UTR variant of the high-expression gene. Optionally, the artificial nucleic acid molecule may further comprise, for example, a 5 '-end cap structure (Cap), a PolyA tail. The 5 'UTR and the 3' UTR have regulating effects on translation and stability of nucleic acid molecules, so that the 5 'UTR, the 3' UTR and variants thereof are selected from high-expression genes, the nucleic acid molecules can be further stabilized and are not easy to degrade, and the amount of protein or polypeptide obtained by translation of the nucleic acid molecules can be increased. The invention also provides methods for making, delivering, and using such artificial nucleic acid molecules, as well as the use of the artificial nucleic acid molecules for the treatment and / or prevention of related diseases or disorders.

The invention provides an UTR (Untranslated Region) element H2202 P1-G as well as a construction method and application thereof, and relates to the technical field of mRNA (messenger ribonucleic acid). According to the present invention, the ribosome load prediction and the secondary structure optimization are performed on the natural 5 'UTR of the HIV TAT 202 gene through the BaidleHelix platform, and the obtained HTAT 202 P1 sequence avoids the inhibitory hairpin structure so as to significantly improve the luciferase expression quantity compared to the natural UTR; an ncRNA sequence without a secondary structure is introduced on the basis of the HTAT 202 P1, translation inhibition of a 5 'cap region is further relieved, and the protein expression quantity of the constructed H2202 P1-G mutant (the DNA sequence of the H2202 P1-G is as shown in SEQ NO 1, and the RNA sequence is as shown in SEQ NO 2) is further improved.

Recombinant NK cells, and especially recombinant NK-92 cells express a chimeric antigen receptor (CAR) having an intracellular domain of FcεRIγ. Notably, CAR constructs with an intracellular domain of FcεRIγ had a substantially prolonged duration of expression and significantly extended cytotoxicity over time. The CAR may be expressed from RNA and DNA, preferably as a tricistronic construct that further encodes CD16 and a cytokine to confer autocrine growth support. Advantageously, such constructs also enable high levels of transfection and expression of the recombinant proteins and provide a convenient selection marker to facilitate rapid production of recombinant NK / NK-92 cells.

The invention discloses a bovine I-type alpha interferon-ferritin fusion protein, a mutant thereof, a preparation method and an application of the bovine I-type alpha interferon-ferritin fusion protein. The bovine I-type alpha interferon is fused with a ferritin subunit, and interferon molecules are highly repeatedly and orderly displayed on the surface of a ferritin nanocage by utilizing the self-assembly characteristic of ferritin, so that the expression level, the structural stability and the antiviral activity of the interferon are remarkably improved. The fusion protein is further subjected to single-site or multi-site rational design mutation, and a mutant with significantly improved antiviral activity and stability is obtained. According to the invention, a silkworm or insect cell eukaryotic expression system is adopted to express the fusion protein or the mutant thereof, and the expression system is safe to operate, simple and convenient in procedure, low in cost and extremely beneficial to large-scale industrial production; the prepared fusion protein or mutant nanoparticles have application prospects in preparation of drugs or reagents for preventing or treating bovine viral diseases.

The invention relates to the technical field of cytology, in particular to a grass carp brain astrocyte line and application thereof, the grass carp brain astrocyte line is preserved in China Center for Type Culture Collection on May 7, 2025, and the preservation number of the grass carp brain astrocyte line is CCTCC NO: C2025149. The grass carp brain astroglia cell line provided by the invention has the capability of efficiently proliferating GCRV-II, and the virus titer of the GCRV-II replicated in the cell line at least can reach 1.38 * 10 < 8 > pfu / mL or above; after the GCRV-II is blindly passed for 5 generations in a grass carp astroglia cell line, the grass carp can still have typical bleeding symptoms and death due to the virus. And the exogenous plasmid transfected grass carp brain astroglia cell line has similar transfection efficiency to commercial grass carp kidney cells. Therefore, the invention lays an important foundation for deep research of pathogenic mechanism of GCRV-II, vaccine preparation, antiviral drug screening and prevention and control of grass carp viral hemorrhagic disease.

The invention provides a solid oral dosage form comprising tenofovir alafenamide or a pharmaceutically acceptable salt thereof, and emtricitabine or a pharmaceutically acceptable salt thereof.

Compounds are provided having the following structure:or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein a, b, c, d, G1, G2, L1, L2, R1a, R1b, R2a, R2b, R3a, R3b, R4a, R4b, R5, R6, R7, R8 and X are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, nanoparticles comprising the compounds and methods for their use and preparation are also provided.

The invention provides an UTR element NHP1 as well as a construction method and application thereof, and relates to the technical field of mRNA. A 5 'UTR with a good expression effect is designed by integrating dominant sequences of a human high-expression gene and a pathogen natural UTR, a chimeric structure NHP1 with high ribosome load is predicted through a calculation model, a DNA sequence of the NHP1 is as shown in SEQ NO 1, and an RNA sequence of the NHP1 is as shown in SEQ NO 2; an EGFP report system is adopted on the DNA level to rapidly screen UTR; the translation efficiency is quantitatively evaluated on the RNA level through luciferase mRNA (N1-methyl pseudouridine modification); and the particle size is controlled by a microfluidic technology, so that the optimized UTR-mRNA is efficiently expressed after being delivered.

The invention discloses an antibacterial peptide and application thereof, and belongs to the technical field of biology. The antibacterial peptide with an inhibition effect on various clinically common pathogenic microorganisms is obtained, and the antibacterial peptide comprises gram-negative bacteria such as escherichia coli, klebsiella pneumoniae, pseudomonas aeruginosa, acinetobacter baumannii, vibrio parahaemolyticus, salmonella gallinarum, salmonella typhimurium and enterobacter sakazakii, and gram-positive bacteria. The antibacterial peptide provided by the invention can be used as an antibacterial peptide, such as staphylococcus aureus, listeria monocytogenes and bacillus cereus, and the antibacterial peptide provided by the invention is novel in structure and easy to prepare.

The invention discloses a monoclonal antibody BY017 combined with African swine fever virus P30 protein and application of the monoclonal antibody BY017. The invention provides an IgG antibody which is composed of a light chain and a heavy chain. CDR1, CDR2 and CDR3 in the heavy chain variable region are sequentially shown as the 47 to 54 , the 72 to 79 and the 118 to 126 in SEQ ID NO: 1; cDR1, CDR2 and CDR3 in a light chain variable region are sequentially as shown in the 49 to 60 , the 78 to 80 and the 117 to 124 in SEQ ID NO: 3. The invention also protects the application of any one of the IgG antibodies in preparation of products. The product has the functions that the product is used for being combined with an African swine fever virus P30 protein fragment; the antibody is used for binding African swine fever virus P30 protein; the antibody is used for binding African swine fever virus. The IgG antibody provided by the invention can be used for multiple purposes of western blot, immunohistochemistry, flow cytometry, ELISA (Enzyme-Linked Immunosorbent Assay) and the like, and can be used as an important tool for ASFV detection and structural analysis of P30 protein of ASFV detection.

The present invention relates to the field of lentiviral delivery. Specifically provided are a mutated vesicular virus envelope protein and the use thereof in lentiviral vector packaging.

The invention discloses a self-replicating RNA (Ribonucleic Acid) molecule, a porcine rotavirus RNA vaccine and application thereof, and relates to the technical field of vaccines. According to the present invention, the coding sequence of the porcine rotavirus G9P23 type VP4 protein is optimized, such that the fact that the saRNA prepared by using the nucleotide sequence represented by the SEQ ID NO: 10 can secrete the high porcine rotavirus G9P23 type VP4 protein antigen after the cell transfection is found; after the optimized porcine rotavirus G9P23 type VP4 protein is used for immunizing experimental animals, the level of neutralizing antibodies generated by the animals can be improved, and the challenge protection effect is enhanced. Therefore, the nucleic acid molecule provided by the invention can be used for developing drugs and vaccines for causing protective immune response in experimental animal bodies. Compared with a traditional vaccine, the vaccine provided by the invention has good immunogenicity and safety, and has a good application prospect.

The invention discloses a grass carp gamma interferon fusion protein as well as a mutant, a coding gene and application thereof. In order to improve the expression quantity or expression efficiency of the grass carp gamma interferon, codon optimization and mutation are carried out on the coding gene of the grass carp gamma interferon to obtain the grass carp gamma interferon mutant. The fusion protein is further obtained by connecting the grass carp gamma interferon mutant with the C end of the grass carp ferritin heavy chain subunit of which the last 17 amino acids are removed through a connecting peptide. In order to further improve the antiviral activity of the fusion protein, the obtained fusion protein is subjected to single-point mutation, and the titer of the fusion protein is remarkably improved. The fusion protein is expressed by a silkworm cell eukaryotic expression system, and the fusion protein shows a conformation suitable for the interferon to play functions based on the ferritin self-assembly characteristic, so that the titer of the interferon in a host is effectively improved, and the in-vivo and in-vitro half-life period of the interferon is prolonged. The invention has application prospects in preparation of drugs or reagents for preventing or treating viral diseases of grass carp and the like.

The invention relates to novel compositions and methods of using maribavir which enhance its effectiveness in medical therapy, as well as to maribavir isomers and methods of use thereof for counteracting the potentially adverse effects of maribavir isomerization in vivo in the event it occurs.

The invention discloses a novel application of an RNF6 gene, namely, an application of screening a medicine for preventing and / or treating Zika virus infection, aiming at inhibiting expression of the RNF6 gene or knocking out the RNF6 gene. A series of functional experiments prove that the RNF6 gene promotes the replication of the Zika virus, and the purpose of reducing the replication of the Zika virus can be achieved by using an expression inhibitor of the RNF6 gene or knocking out the RNF6 gene; experimental results show that the RNF6 gene can be used as a potential target for preventing and / or treating Zika virus infection, and a new direction is provided for development of drugs for preventing and / or treating Zika virus infection targeting the RNF6 gene in the future.

The invention relates to a CHO-S cell strain capable of stably expressing H5N1 hemagglutinin protein and a construction method of the CHO-S cell strain, and belongs to the field of bioengineering.H5N1 hemagglutinin protein expression plasmids are obtained in an in-vitro synthesis and seamless cloning mode, 293T cells are transfected through the H5N1 hemagglutinin protein expression plasmids, and it is proved that the H5N1 hemagglutinin protein is expressed; the CHO-S cell strain capable of stably expressing the H5N1 hemagglutinin protein is obtained by transfecting CHO-S cells by using the H5N1 hemagglutinin protein expression plasmids and carrying out multiple rounds of cloning and screening, so that a basis is provided for obtaining H5N1 recombinant protein influenza vaccines.

A method of treating or inhibiting a viral infection in a human subject, such as a SARS-CoV-2 infection, involves inhibiting in vivo the expression or activity of one or a combination of the subject's genes required for viral infection. Single genes or subsets of genes for inhibition of activity or expression are selected from certain identified genes. Methods of administration of certain known small molecules or other therapeutics which mimic loss of function of the identified genes are provided. Similar methods for conducting screens of host genes required for viral infection are shown.

The invention discloses an application of CD4 + CD8 + double-positive T cells in improvement of poor immune reconstitution of HIV (human immunodeficiency virus) infected patients, and relates to the technical field of biological pharmacy, in particular to the application of preparation of the CD4 + CD8 + double-positive T cells in the poor immune reconstitution of the HIV infected patients. The number of peripheral blood CD4 + T cells of HIV infected patients is increased, the immune system of the patients is improved, and the probability of possible opportunity infection and other related diseases of the patients is reduced, so that the morbidity and mortality of the patients are reduced.

The invention relates to mRNA comprising lipid nanoparticles and their medical uses. The lipid nanoparticles of the present invention comprise a cationic lipid according to formula (I), (II) or (III) and / or a PEG lipid according to formula (IV), as well as an mRNA compound comprising an mRNA sequence encoding an antigenic peptide or protein. The invention further relates to the use of said lipid nanoparticles as vaccines or medicaments, in particular with respect to influenza or rabies vaccination.

Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins of Cas9 and nucleic acid editing proteins or protein domains, e.g., deaminase domains, are provided. In some embodiments, methods for targeted nucleic acid editing are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of Cas9 and nucleic acid editing proteins or domains, are provided.

The invention discloses a specific antibody MR-34 for targeting a coronavirus MERS-CoV spike protein RBD (Radial Basis Disease). The sequences of the CDRs of the antibody disclosed by the invention are as shown in SEQ ID NO. 1 to SEQ ID NO. 6. The antibody provided by the invention contains CDRs with a specific sequence, and can be specifically combined with an MERS-CoV spike protein RBD structural domain. The antibody provided by the invention is strong in targeting property and high in binding activity, and the antibody prepared by the preparation method provided by the invention is high in purity and can be prepared on a large scale. On the whole, the antibody disclosed by the invention can be used for developing and optimizing an MERS-CoV infection detection method.

The invention discloses preparation of a whey protein peptide mixture with immune and muscle-building effects, and relates to the technical field of food processing and bioengineering. The neutral protease is adopted and the pH is adjusted, so that the enzymolysis efficiency is effectively improved, and the enzymolysis time is greatly shortened; meanwhile, the whey protein peptide which is uniform in molecular weight distribution, free of peculiar smell and good in thermal stability is successfully prepared by accurately controlling enzymolysis conditions and combining microbial fermentation. The protein peptide can effectively improve thymus indexes and spleen indexes, enhance the proliferation capacity of splenic lymphocytes and the activity of NK cells, play an excellent immune regulation role and have a remarkable muscle building effect. The preparation process has the advantages of high efficiency, low cost, simplicity, convenience and the like, gives consideration to high quality and high functionality of the product, and has great application value.

The invention belongs to the technical field of biological detection, and particularly relates to a monoclonal antibody 1D3 for detecting a porcine epidemic diarrhea virus antibody and application of the monoclonal antibody 1D3. The CDR sequences of the heavy chain variable region are respectively shown as SEQ ID NO.1-3, and the CDR sequences of the light chain variable region are respectively shown as SEQ ID NO.4-6. The antibody can specifically recognize PEDV / S1 protein, binding of the antibody can be competitively blocked by a PEDV specific neutralizing antibody in serum, and the antibody is suitable for establishing a blocking ELISA method. A detection tool based on the antibody has high specificity and sensitivity, and the blocking rate to PEDV positive serum is higher than 50%. The invention can be used for preparing a detection kit or evaluating the immune effect of a vaccine, and provides an efficient and accurate technical means for PEDV infection diagnosis and immune monitoring.

The invention belongs to the technical field of biology, and discloses application of a mycoplasma hyopneumoniae Ebh GA protein in preparation of mycoplasma hyopneumoniae or a multi-combined vaccine containing the mycoplasma hyopneumoniae. The applicant screens out the Ebh GA protein with immunogenicity from the mycoplasma hyopneumoniae for the first time, the Ebh GA protein is shown in SEQ ID NO.7 and can be used as a mycoplasma hyopneumoniae subunit vaccine, and therefore the applicant screens out the protein with immunogenicity of other pathogenic bacteria at the same time and combines the protein with the protein into a quadruple subunit vaccine. The antigens of the obtained quadruple vaccine have a synergistic effect, and compared with a single dose, the quadruple vaccine can enhance the immune effect of the quadruple vaccine.

The invention belongs to the technical field of biology, and particularly relates to a mouse hepatitis virus antibody or an antigen binding fragment thereof as well as a preparation method and application thereof. The antibody or the antigen binding fragment thereof can specifically recognize and bind to the mouse hepatitis virus or the NSP3 protein thereof, and has good affinity with the mouse hepatitis virus or the NSP3 protein thereof; the kit can be used for preparing products for diagnosing, preventing and / or treating mouse hepatitis virus infection or diseases caused by the mouse hepatitis virus infection, detecting existence or level of mouse hepatitis virus or NSP3 protein in a sample, screening medicines for preventing and / or treating the mouse hepatitis virus infection or the diseases caused by the mouse hepatitis virus infection, and carrying out basic research and / or vaccine development.

The invention relates to the technical field of biological medicine, in particular to a ferroptosis inhibition type phospholipid-like material and application thereof. The ferroptosis inhibition type phospholipid-like material is one of the following structural general formulas (1)-(5). The biomimetic phospholipid-like ferroptosis inhibitor has a long retention characteristic in main positions (cell membranes, endoplasmic reticulum and other organelle membranes) of cell ferroptosis, so that the ferroptosis inhibition efficiency is remarkably improved. The novel phospholipid-like material not only can be used as an active drug molecule, but also can be used as a pharmaceutic adjuvant for constructing drug delivery carriers such as lipidosome and micelle and implant coatings, and is suitable for various administration routes such as oral administration, injection and local administration. The novel biomimetic ferroptosis inhibitor can efficiently relieve cell ferroptosis and has a wide application prospect in the field of treating or retarding ferroptosis-related diseases.

The present disclosure relates generally to multisubunit nucleic acids comprising a plurality of polynucleotide sequences, wherein each polynucleotide sequence of the plurality comprises a target sequence, a linker sequence, and a self-assembling sequence, or a linker sequence, a target sequence, a linker sequence, and a self-assembling sequence, or a combination thereof, wherein each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence, and wherein the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality, wherein the target sequence is obtained or derived from a respiratory syncytial virus, a metapneumovirus, a human parainfluenza virus, or a combination thereof. The multisubunit nucleic acid encodes a multisubunit peptide.

The invention provides a double-target degradation molecule based on a functionalized nucleic acid connexon and application thereof, and relates to the technical field of biological medicine, the double-target degradation molecule comprises an E3 ubiquitin ligase ligand at one end, a first target protein ligand at the other end, and the functionalized nucleic acid connexon located between the E3 ubiquitin ligase ligand and the first target protein ligand; the functionalized nucleic acid linker is a nucleotide sequence capable of specifically recognizing and combining a second target protein or a coding gene thereof, so that the protein level degradation of the first target protein and the nucleic acid level or expression level inhibition of the second target protein / gene are realized in the same molecule. Functionalized nucleic acid and a PROTAC strategy are organically combined, single-molecule double-target collaborative intervention is achieved, targeting efficiency and treatment potential are improved, higher flexibility and expandability are provided in synthesis and design, and a new molecular platform and technical route are provided for multi-target accurate treatment.

This disclosure relates to fusion proteins comprising one or more EBV polypeptides and a ferritin protein, and their use in eliciting antibodies against EBV.