1381 results about "Coronavirus" patented technology

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 relates to a PLpro protease small-molecule inhibitor for treating or preventing coronavirus infection and application of the PLpro protease small-molecule inhibitor. Specifically, the invention relates to a compound shown as a formula (I) or an isotope labeled compound thereof, or an optical isomer, a geometric isomer, a tautomer or an isomer mixture thereof, or a pharmaceutically acceptable salt thereof, or a prodrug thereof, or a metabolite thereof, and the use thereof in the preparation of a medicament for treating or preventing coronavirus infection or diseases or symptoms caused by coronavirus.

The invention provides a subunit fusion protein RBD-Fc on the surface of a porcine D-type coronavirus and a preparation method and application thereof, the preparation method comprises the following steps: 1) cloning a gene sequence as shown in SEQ ID NO.5 into a eukaryotic expression vector to obtain a recombinant plasmid containing a fusion protein RBD-Fc coding gene; (2) transfecting a recombinant plasmid containing the fusion protein RBD-Fc coding gene into an expression cell; 3) culturing, screening and domesticating the expression cells in the step 2) to obtain a highly expressed cell strain; and 4) fermenting and culturing the cell strain in the step 3), and purifying to obtain the subunit fusion protein RBD-Fc. According to the present invention, the RBD-Fc can be subjected to mass soluble expression, the protein is stable, the problems that the porcine D-coronavirus surface S protein cannot be subjected to large-scale expression and the like in the prior art are solved, the preparation method is simple, and the cost is low.

The invention belongs to the technical field of biological pharmacy, and particularly relates to influenza virus-like particles for chimeric expression of new coronavirus RBD protein as well as a preparation method and application of the influenza virus-like particles. The virus-like particle is prepared by embedding fusion protein on the surface of influenza virus M1, and the fusion protein comprises an HA2 segment of HA protein of influenza virus, an extracellular functional region of M2e matrix protein, a conserved region short peptide of nucleoprotein, and RBD tandem protein with mutated five sites of 417, 452, 478, 484 and 501 of new coronavirus; the virus-like particles can be used for preventing specific influenza and new crowns; the preparation method of the virus-like particles is simple and low in cost, the virus-like particles are good in immunogenicity and cross protectiveness, the preparation requirements of large-scale influenza vaccines can be met, the biological safety is high, and the immunity of an organism to various influenza viruses and new coronal viruses can be stimulated.

The application provides a virus combined detection immunochromatography test paper, a detection pen and a detection product, and relates to the technical field of immunochromatography test paper. The virus combined detection immunochromatography test paper can detect the novel coronavirus, the influenza A virus and the influenza B virus in a three-in-one manner. The sample binding pad of the immunochromatography test paper is coated with labeled antibodies, including a first influenza A virus antibody, a first influenza B virus antibody, a first novel coronavirus antibody and a first human internal reference protein antibody, and each labeled antibody is labeled with a different color of label. The immunochromatography test paper adopts a double-antibody sandwich principle, and the second influenza A virus antibody, the second influenza B virus antibody and the second novel coronavirus antibody are coated on different detection lines in the detection area. The immunochromatography test paper and the detection pen solve the problems of complex operation and difficult interpretation of the three-in-one detection product of the novel coronavirus, the influenza A virus and the influenza B virus in the prior art.

The invention discloses a novel coronavirus neutralizing antibody, a detection kit and application of the novel coronavirus neutralizing antibody. The amino acid sequence of a heavy chain variable region of the neutralizing antibody is shown as SEQ ID No.1, and the amino acid sequence of a light chain variable region of the neutralizing antibody is shown as SEQ ID No.2. The antibody with mature affinity is screened through bioinformatics analysis of a single B cell, the antibody screening process is optimized by combining single cell RNA sequencing, VDJ rearrangement analysis and somatic cell hypermutation research, blindness of a traditional method is avoided, and the accuracy and effectiveness of antibody screening are improved. According to the neutralizing antibody GR75 provided by the invention, a heavy chain variable region and a light chain variable region of the neutralizing antibody GR75 can be specifically combined with an RBD structural domain of the SARS-CoV-2 and an S-Trimer structural domain of an Omicro variant, so that a broad-spectrum neutralizing effect on the SARS-CoV-2 virus and the variant thereof is realized. The binding activity of the antibody GR75 to S-Trimer and RBD under 2-fold and 300-fold dilution conditions is obviously superior to that of other antibodies, which indicates that the antibody GR75 has high affinity and dilution stability and is suitable for clinical large-dose administration.

The invention discloses a novel coronavirus neutralizing antibody GR46, a detection kit and application of the novel coronavirus neutralizing antibody GR46. The amino acid sequence of a heavy chain variable region of the neutralizing antibody is shown as SEQ ID No.1, and the amino acid sequence of a light chain variable region of the neutralizing antibody is shown as SEQ ID No.2. The antibody with mature affinity is screened through bioinformatics analysis of a single B cell, the antibody screening process is optimized by combining single cell RNA sequencing, VDJ rearrangement analysis and somatic cell hypermutation research, blindness of a traditional method is avoided, and the accuracy and effectiveness of antibody screening are improved. According to the neutralizing antibody GR46 provided by the invention, a heavy chain variable region and a light chain variable region of the neutralizing antibody GR46 can be specifically combined with an RBD structural domain of the SARS-CoV-2 and an S-Trimer structural domain of an Omicro variant, so that a broad-spectrum neutralizing effect on the SARS-CoV-2 virus and the variant thereof is realized. The binding activity of the antibody GR46 to S-Trimer and RBD under 2-time and 300-time dilution conditions is obviously superior to that of other antibodies, which indicates that the antibody GR46 has high affinity and dilution stability and is suitable for clinical large-dose administration.

The invention relates to the technical field of biological medicine, in particular to a monoclonal antibody of bovine coronavirus S2 protein, an epitope of the monoclonal antibody and application of the epitope. The invention provides a hybridoma cell strain (preservation number: CCTCC (China Center For Type Culture Collection) NO: C202510). The cell strain can secrete a monoclonal antibody which is targeted and combined with bovine coronavirus S2 protein; the amino acid sequence of the epitope identified by the monoclonal antibody is shown as SEQ ID NO: 1. Experiments prove that the monoclonal antibody has neutralizing activity, and the targeting epitope of the monoclonal antibody is a key neutralizing epitope. The invention provides a new strategy and tool for antibody drug and vaccine research and development as well as diagnosis and detection of the bovine coronavirus.

Apparatuses, systems and methods are provided for treating pulmonary tissues via delivery of energy, generally characterized by high voltage pulses, to target tissue using a pulmonary tissue modification system (e.g., an energy delivery catheter system). Example pulmonary tissues include, without limitation, those within the respiratory tract, particularly the epithelium (the goblet cells, ciliated pseudostratified columnar epithelial cells, and basal cells), lamina propria, submucosa, submucosal glands, basement membrane, smooth muscle, cartilage, nerves, pathogens resident near or within the tissue, or a combination of any of these. The systems may be used to treat pathogens, such as bacteria and viruses, particularly coronaviruses.

The invention discloses a porcine delta coronavirus monoclonal antibody and application thereof in preparation of an antigen detection test strip. The detection test strip comprises a polyvinyl chloride bottom plate on the lowest layer, and a sample pad, a conjugate pad, a nitrocellulose membrane and a water absorption pad are sequentially laid on the polyvinyl chloride bottom plate in the flowing direction; the sample pad is partially overlapped on the combination pad, and the combination pad and the water absorption pad are respectively overlapped on two sides of the nitrocellulose membrane; a detection line and a quality control line are arranged on the nitrocellulose membrane along the flowing direction; an antibody marked by red latex microspheres is sprayed on the combination pad, a coated antibody is sprayed on the detection line, and coated commercial goat anti-mouse IgG is sprayed on the quality control line. The test strip adopts a double-antibody sandwich method for detection, and has the advantages of high detection speed, high sensitivity, strong specificity and the like. The detection result is visual, clear and easy to interpret; the detection process does not need any instrument and equipment, operators do not need professional training, operation is easy and convenient, and the method is particularly suitable for on-site rapid diagnosis.

The present invention uses ex vivo human airway cultures to assess the human transmissibility and replication competence of influenza and coronavirus strains. By comparing pandemic influenza A subtype H1N1 and highly pathogenic avian influenza H5N1 as reference strains, the transmissibility risk of various viruses was evaluated and categorized. Additionally, an in vitro model evaluated virus-induced impairment of alveolar fluid clearance (AFC) as an indicator of disease severity. The study revealed correlations between bronchus viral replication, human transmission, AFC impairment, and clinical disease severity across different influenza and coronavirus strains.

The invention belongs to the technical field of biological medicine, and particularly relates to application of anethomycin in preparation of medicine for inhibiting cysteine protease activity. The invention discovers that anethomycin has the function of inhibiting the activity of virus cysteine protease, especially 3C or 3CL protease, for the first time. Molecular docking proves that anethomycin can effectively bind to the catalytic activity center of Senecavirus (SVA) 3C protease. An in-vitro FRET enzyme activity experiment proves that the inhibition rate of 50 [mu] M of anethomycin on SVA 3C protease reaches up to 88.5%. Cellular level experiments show that the anethomycin can significantly inhibit replication of SVA viruses, shows broad-spectrum antiviral activity on various viruses such as encephalomyocarditis viruses (EMCV), porcine reproductive and respiratory syndrome viruses (PRRSV) and porcine deltacoronaviruses (PDCoV), and is low in cytotoxicity and high in selectivity index (SI).

The invention discloses a cell membrane protein replacement type oncolytic virus vector and application thereof. The cell membrane protein replacement type oncolytic virus vector is rhabdoviridae virus, and a nucleotide sequence for coding G protein in a genome of the rhabdoviridae virus is replaced by a nucleotide sequence for coding an antibody and a nucleotide sequence for coding a spike protein truncation of coronavirus. The invention also discloses a construction method of the cell membrane protein replacement type oncolytic virus vector for expressing the antibody, the non-replicated virus vector is used for expressing the antibody sequence for the first time, and meanwhile, the novel coronavirus cell membrane protein is embedded into the virus surface, so that the cell membrane protein replacement type oncolytic virus vector can be rapidly produced in a suspension cell in a large scale; through removal of virus cell membrane protein genes, the virus cell membrane protein genes cannot be continuously replicated in vivo, so that the safety of the virus cell membrane protein genes is ensured, the tumor immunosuppression condition is improved, and an organism can be stimulated to generate a neutralizing antibody for resisting new coronavirus while tumor cells are killed.

The invention belongs to the technical field of antibodies, and discloses an antibody for resisting novel coronavirus envelope protein or an antigen binding fragment thereof and application thereof. The antibody or the antigen binding fragment thereof comprises a heavy chain and a light chain; a heavy chain of the antibody or the antigen binding fragment thereof comprises: a heavy chain variable region, wherein the heavy chain variable region comprises CDR-H1, CDR-H2 and CDR-H3; a light chain of the antibody or the antigen binding fragment thereof comprises a light chain variable region, and the light chain variable region comprises CDR-L1, CDR-L2 and CDR-L3. The antibody or the antigen binding fragment thereof can be used for detecting the existence or the level of the novel coronavirus envelope protein in a sample, detecting the novel coronavirus and diagnosing diseases related to novel coronavirus infection.

The invention discloses a method for quickly rescuing bovine coronavirus epidemic strains and application of the method. The bovine coronavirus SHZ isolate is subjected to efficient segmented cloning, the obtained segment and a Linker sequence are subjected to a cyclic polymerase extension reaction, and the obtained reaction product can be directly transfected to 293T cells for virus packaging without purification. Different from a traditional method, the method does not need to amplify full-length virus cDNA clone by means of bacteria and yeast, but directly obtains a sufficient amount of preliminary products through PCR, and avoids the problems of instability and low efficiency when partial sequences of a virus genome proliferate in a bacteria or yeast host. By adopting the reverse genetic system, the recombinant bovine coronavirus expressing the foreign protein is successfully rescued, a brand new technical platform is provided for dynamic visualization research of in-vivo and in-vitro replication of the virus, and an efficient and flexible tool is also provided for virology research, development of virus vector vaccines and screening of antiviral drugs.

The present disclosure relates to compounds of Formula (I):and pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, useful in the treatment of treating viral infections, for example, coronaviridae infections.

An mRNA vaccine encapsulated with lipid nanoparticles for PDCoV, a preparation method and an application thereof are provided, and the mRNA vaccine for PDCoV includes at least one of sequences as described in SEQ ID NO: 1-2; the lipid nanoparticle-encapsulated mRNA vaccines includes the mRNA vaccine, and lipids for encapsulating the mRNA vaccine, and the lipids are formed by mixing ionizable liposome, distearoyl phosphatidylcholine, cholesterol and PEG liposome.

The present disclosure provides compositions and methods comprising a selective inhibitor of Rho-related coiled-coil kinase 2 (ROCK2) for use in the treatment of viral infections, particularly coronavirus infections such as SARS-CoV-2, and in the treatment of sequelae caused by the viral infections, including sequelae caused by coronavirus infections.

The invention belongs to the technical field of biological detection, and particularly relates to a monoclonal antibody combination for detecting feline coronavirus NP protein and application of the monoclonal antibody combination. The combination is composed of monoclonal antibodies 3C6 and 6H9, 3C6 serves as a coating antibody, 6H9 is used for colloidal gold labeling, and efficient and specific sandwich detection of feline coronavirus NP protein can be achieved. According to the invention, the monoclonal antibody combination is correspondingly applied to an immunodetection platform, and a rapid detection test strip or test paper card based on a colloidal gold immunochromatography technology is constructed. The test paper has high sensitivity to FECV-NP and FIBV-NP recombinant proteins, has no cross reaction with other proteins, and is suitable for rapid and on-site detection.

The invention relates to the technical field of genetic engineering, and particularly provides a multi-linked quality control product for quality control of a novel coronavirus nucleic acid detection laboratory and a preparation method of the multi-linked quality control product. The multi-linked quality control product is a multi-component composite system and is formed by mixing three substances, namely pseudovirus, target gene RNA (Ribonucleic Acid) molecules and internal standard plasmid DNA (Deoxyribose Nucleic Acid). Wherein the pseudovirus is pseudovirus particles of novel coronavirus ORF1ab gene RNA (Ribonucleic Acid) wrapped by a vesicular stomatitis virus vector and is used for monitoring virus nucleic acid extraction; the target gene RNA molecule is a novel coronavirus N gene RNA molecule and can monitor the reverse transcriptase activity; the internal standard plasmid is plasmid DNA of a human housekeeping gene RPP30, and whether inhibition or failure exists in an amplification link is monitored. According to the method, the whole process of nucleic acid extraction, reverse transcription and amplification is synchronously and hierarchically monitored, the monitoring blind area of a traditional single-component quality control product is solved, and the accuracy and efficiency of laboratory detection quality control are remarkably improved.

The present invention relates to treatment of COVID-19 and methods thereof. A vaccine composition for inducing immunity against coronavirus in a subject comprises a recombinant nucleic acid encoding an N-ETSD, which is a modified nucleocapsid protein comprising an endosomal targeting sequence, and / or a recombinant nucleic acid encoding an S-fusion, which is a modified spike protein with improved surface expression. The vaccines can be formulated as recombinant nucleic acids, recombinant yeasts, and / or recombinant viruses, such as adenoviruses, and can be administered via injection and / or mucosal delivery.

The invention provides a porcine deltacoronavirus S1 protein nanoparticle vaccine CTDnps and application thereof, and belongs to the technical field of vaccine preparation. The PDCoV S1 protein C-terminal structural domain nanoparticle vaccine capable of being self-assembled, provided by the invention, comprises ferritin and a PDCoV S1 protein C-terminal structural domain, the amino acid sequence of the ferritin is as shown in SEQ ID NO.1, and the amino acid sequence of the PDCoV S1 protein C-terminal structural domain is as shown in SEQ ID NO.2. The PDCoV S1 protein C-terminal structural domain nanoparticle vaccine capable of being self-assembled comprises the ferritin and the PDCoV S1 protein C-terminal structural domain. The PDCoV S1 protein C-terminal structural domain nanoparticle vaccine (S1CTD-Fer) constructed by the invention can be self-assembled to form ferritin-like cage-shaped nanoparticles, and the hydrodynamic diameter of the cage-shaped nanoparticles is obviously greater than that of natural ferritin nanoparticles. Compared with the S1CTD, the S1CTD-Fel based on the ferritin carrier can obviously enhance the immunogenicity of the S1CTD, can obviously enhance the uptake efficiency of antigen presenting cells, and is high in safety.

The invention discloses a porcine delta coronavirus spike protein monoclonal antibody, an antigen epitope peptide and application, and belongs to the technical field of biology. The antibody comprises a light chain variable region and a heavy chain variable region, the amino acid sequence of the light chain variable region is as shown in SEQ ID No.1, and the amino acid sequence of the heavy chain variable region is as shown in SEQ ID No.3. According to the invention, a highly conservative linear B cell epitope (the amino acid sequence is DFGEARLD) of a PDCoV spike protein receptor binding domain (S-RBD) and a neutralizing monoclonal antibody capable of being specifically bound to the epitope are identified for the first time. The epitope peptide and the monoclonal antibody provided by the invention can be used for immunological detection and serological investigation of the PDCoV.

The present invention pertains to anti-coronaviral compounds. The disclosure includes a method for preventing and / or treating a coronavirus infection through the inhibition of a cysteine protease in a virus, particularly SARS-COV-2. Also provided includes the composition / pharmaceutical composition for preventing and / or treating a coronavirus infection comprising any of the compounds, pharmaceutically acceptable salt thereof, or its mixture, and the use of the compounds.

Pan-coronavirus vaccines for inducing efficient, powerful and long-lasting protection against all Coronaviruses infections and diseases, comprising multiple highly conserved large sequences which may comprise one or more conserved B, CD4 and CDS T cell epitopes that help provide multiple targets for the body to develop an immune response for preventing a Coronavirus infection and / or disease. In certain embodiments, the large sequences are conserved proteins or large sequences, e.g., sequences that are highly conserved among human coronaviruses and / or animal coronaviruses (e.g., coronaviruses isolated from animals susceptible to coronavirus infections).

The present disclosure relates to a method of treating one or more inflammation conditions induced by a coronavirus infection in a subject in need thereof, comprising administering a pharmaceutical composition comprising a compound of Formula I or Formula II:whereinR1 is halogen, OH, or —OC(O)C1-5alkylR2 and R3 are each independently selected from CO2R4 and CH2OR5;R4 is Li, Na, K, H, C1-5alkyl, or —CH2CO(C1-5alkyl); andR5 is H or —C(O)(C1-5alkyl),or a pharmaceutically acceptable salt thereof.

The invention provides application of Ulixertinib in treatment of lung tissue inflammation caused by novel coronavirus, and the Ulixertinib can effectively relieve the lung inflammatory infiltration degree after infection of the novel coronavirus, reduce the expression level of cytokines, chemotactic factors or NETs related proteins and inhibit formation of NETs. The invention provides a brand new treatment strategy for novel coronavirus infection, especially severe lung tissue inflammation caused by multiple infection of novel coronavirus.

The invention belongs to the technical field of biological pharmacy, and particularly relates to an anti-coronavirus medicine and application. According to the application disclosed by the embodiment of the invention, experiments prove that the punicalagin and the punicalagin respectively have strong binding force to SARS-CoV-2 main protease Mpro and have a remarkable inhibition effect on SARS-CoV-2 virus replication, so that the punicalagin and the punicalagin can be used as novel SARS-CoV-2 inhibitors. Therefore, punicalagin and / or punicalagin can be used for preparing products for inhibiting novel coronavirus.

Waning immunity induced by first-generation Spike-alone-based COVID-19 has failed to prevent immune escape by many variants of concern (VOCs) that emerged from 2020 to 2024, resulting in a prolonged COVID-19 pandemic. Thus, a next-generation Coronavirus (CoV) vaccine incorporating highly conserved non-Spike SARS-CoV-2 antigens is described herein. Conserved non-Spike T cell antigens in combination with a Spike antigen encapsulated in lipid nanoparticles: (i) Induced high frequencies of lung-resident antigen-specific CXCR5+CD4+ T follicular helper cells, GzmB+CD4+ and GzmB+CD8+ cytotoxic T cells, and CD69+IFN-γ+TNFα+CD4+ and CD69+IFN-γ+TNFα+CD8+ effector T cells; and (ii) Reduced viral load and COVID-19-like symptoms caused by various VOCs. The combined antigen / LNP-based pan-CoV vaccine could be rapidly adapted for clinical use to confer broader cross-protective immunity against emerging highly mutated and pathogenic VOCs.

The invention provides a subunit fusion protein tS on the surface of porcine D-type coronavirus as well as a preparation method and application of the subunit fusion protein tS, the preparation method comprises the following steps: 1) cloning a gene sequence as shown in SEQ ID NO.5 into an eukaryotic expression vector to obtain a recombinant plasmid containing a fusion protein tS coding gene; 2) transfecting a recombinant plasmid containing the fusion protein tS coding gene into an expression cell; 3) culturing, screening and domesticating the expression cells in the step 2) to obtain a highly expressed cell strain; and 4) fermenting and culturing the cell strain in the step 3), and purifying to obtain the subunit fusion protein S. The S can be expressed in a large amount in a soluble manner, the protein is stable, the problems that the S protein on the surface of the porcine D-type coronavirus cannot be expressed in a large scale and the like in the prior art are solved, and the preparation method is simple and low in cost.