71 results about "Host protein" patented technology

Disclosed herein are methods, antibodies, and compositions for disrupting an interaction between Galectin-3 (Gal3) and viral proteins, such as proteins of the SARS-CoV-2 virus or other coronaviruses, or viral-associated host proteins. Further disclosed herein are methods, medicaments, and compositions for the treatment of a disease or a disorder in a subject, such as the treatment of a viral infection, or treatment of a fibrosis, such as lung fibrosis, that develop as a sequela of a viral infection, or cytokine release syndrome. Further disclosed herein are methods, medicaments, and compositions for the treatment of an inflammatory disease or disorder, such as inflammation of the lungs or systemic lupus erythematosus, which may be associated with neutrophil activity, in a subject. Also disclosed herein are pharmaceutical antibody formulations for the treatment of a disease, such as a coronavirus infection.

The invention discloses an application of CXCL11 as an antiviral drug, relates to the field of biological medicines, and in particular relates to a protein of an antiviral drug, and the protein as the antiviral drug can inhibit infection and replication of RSV (Respiratory Syndrome Virus). The invention also provides a technical enlightenment for taking a related host protein in a virus infection pathway as an antiviral drug research target, and an application related indication of the CXCL11 protein analogue to clinical symptoms and / or clinical indications caused by severe respiratory syncytial virus infection. The invention further provides an administration route of the CXCL11 serving as an antiviral drug, a dosage range of drug intervention and the like, and finally, the feasibility of the CXCL11 serving as the antiviral drug is further verified through drug intervention application after drug challenge in CXCL11 <- / -> mice.

The invention discloses a preparation method and application of recombinant human-like collagen. The recombinant human-like collagen is fusion protein of collagen and elastin. The preparation method comprises the following steps: taking constructed escherichia coli engineering bacteria, inducing expression of human-like collagen through high-density fermentation, performing high-pressure homogeneous cell disruption after tubular centrifugal collection of fermented thalli, performing acid regulation, flocculating and settling of cell debris and host protein, and controlling pH and conductivity of feed liquid to obtain the human-like collagen. Through ion exchange chromatography purification and ultrafiltration concentration replacement, a human-like collagen stock solution with the liquid phase purity of more than 98% is obtained, and the total yield is more than 75%. Through cell biological activity detection and analysis, the purified human-like collagen has remarkable biological activity of promoting cell migration and adhesion. The whole preparation process developed by the invention is simple and convenient in process, high in yield, easy to amplify and suitable for industrial production of the recombinant human-like collagen, and the prepared protein raw material can be widely applied to the fields of medical beauty and biological medicine.

The present invention relates to the field of biomedicine, and more particularly to a method for purifying an inactivated rabies virus vaccine. The method comprises the following steps: preparing an inactivated rabies virus ultrafiltration concentrate: purifying the inactivated rabies virus ultrafiltration concentrate by chromatography; the chromatography purification specifically comprises the following steps: column cleaning: loading a composite filler into a chromatography column, connecting an AKTA to the chromatography column, cleaning, sterilizing, and setting aside; chromatography operation: equilibrating the chromatography column with PBS buffer; sample loading: loading the inactivated rabies virus ultrafiltration concentrate into the chromatography column, eluting with an eluent, and collecting the eluate corresponding to the absorption peak at an ultraviolet wavelength of 280 nm, which is the purified inactivated rabies virus vaccine; column cleaning; and results showing that the residual protein content is as low as 5.0 ng / ml, the antigen content can reach above 16.0 IU / ml, the host protein removal rate can reach above 99%, and the antigen content recovery rate can reach above 86%.

The invention provides a recombinant foot-and-mouth disease virus strain with high antigen yield as well as a construction method and application thereof, and belongs to the technical field of biology. The invention relates to a recombinant foot-and-mouth disease virus strain, wherein L protein is mutant L protein with 108th amino acid mutated or deleted. According to the invention, overexpression of host protein RAB20 inhibits replication of FMDV, and L protein is degraded through a proteasome pathway, so that virus replication is inhibited; a recombinant foot-and-mouth disease virus strain which is not inhibited by host protein RAB20 to replicate is constructed by mutating a key amino acid site (108) in FMDV L protein, the recombinant virus can be stably passaged, has the characteristic of high virus titer on BHK-21 cells, improves the virus titer and antigen yield, can be used for preparing FMDV vaccines, and can be used for preparing FMDV vaccines. Good application prospects are realized.

The invention relates to a high-temperature-resistant feruloyl esterase liquid as well as a preparation method and application thereof. The preparation method comprises the following steps: (1) constructing a reaction system: suspending recombinant microorganism thalli for expressing high-temperature-resistant feruloyl esterase in a buffer solution with the pH value of 7.0-9.0; (2) ultrasonic cracking and thermal purification: heating the reaction system to 70-85 DEG C under the condition of ultrasonic crushing, and keeping the temperature for 1-8 hours; carrying out structural destruction on the microbial thalli by utilizing ultrasound so as to release intracellular high-temperature-resistant feruloyl esterase, and carrying out denaturation and precipitation on host impure protein by utilizing the thermal stability difference between the high-temperature-resistant feruloyl esterase and the host impure protein; after the high-temperature-resistant feruloyl esterase is subjected to heat treatment in the step (2), the catalytic activity is kept at the temperature of 60 DEG C or above; and (3) obtaining an enzyme solution, namely centrifuging the reaction body fluid subjected to the ultrasonic treatment and the heat treatment in the step (2), and collecting supernate, so as to obtain the high-temperature-resistant feruloyl esterase solution.

The application is a virus and host protein interaction prediction method based on a densely connected convolutional network, comprising the following steps: step 1, preprocessing data; step 2, using a Skip-Gram model in Word2Vec and One-Hot encoding to obtain embedding vectors of amino acids; step 3, constructing a densely connected convolutional network for feature extraction according to a word embedding matrix of the protein; step 4, obtaining average RPM-PSSM feature descriptors through a PSSM feature matrix; step 5, constructing a fully connected neural network for feature extraction according to the feature descriptors; step 6, performing feature fusion through a concatenate operation, and finally using the trained model for prediction. The application performs feature extraction on different features, contains protein evolution information and physicochemical properties, local key information and long-range dependence in the sequence, and better improves the prediction accuracy.

The invention belongs to the field of biology, and particularly relates to construction of a recombinant Seneca virus strain with Seneca virus 2B protein translation block site mutation. The 26th lysine (K) of the 2B protein is found to be a key site for inhibiting the translation of the host protein for the first time, and after the 26th K of the 2B protein is mutated into the alanine (A), the translation retardation phenomenon of the host protein is obviously weakened; secondly, the 26th K of the 2B protein is mutated into A to construct infectious clone, and the recombinant Seneca virus strain rSVA-2B K26A with 2B protein translation retardation site mutation is successfully rescued and obtained, compared with wild type SVA, after the rSVA-2B K26A infects host cells, the translation retardation phenomenon of the host cells is weakened, the expression level of host antiviral inflammatory cytokines is enhanced, and the expression level of the recombinant Seneca virus strain rSVA-2B K26A is improved. The Seneca virus vaccine strain can be used as a potential vaccine candidate strain, and a foundation is laid for developing a novel prevention and control strategy aiming at the Seneca virus.

The invention discloses a rabbit milk host protein detection kit. The rabbit milk host protein detection kit comprises an elisa plate coated with a capture antibody and a detection antibody marked by HRP (horse radish peroxidase), the capture antibody is an antibody obtained by performing Protein G affinity chromatography on serum obtained after sheep is immunized by using non-transgenic skimmed rabbit milk as an immunogen; the detection antibody is obtained by performing immunoaffinity chromatography on serum obtained after sheep is immunized by using non-transgenic skimmed rabbit milk as an immunogen. The kit disclosed by the invention is applied to detection of rabbit milk host protein residues in recombinant protein medicines expressed by a transgenic rabbit breast bioreactor, and has the characteristics of high specificity, high sensitivity, high detection efficiency, capability of simultaneously detecting a plurality of samples, simple used equipment, convenience in operation and low detection cost, and the limit of quantitation reaches 5ng / mL.

Proteases of Group IV (+)ssRNA viruses were found to act on a human sequences in addition to the viral sequences. The identity of the cleavable human sequences is disclosed. Detection of these sequences can act as a diagnostic of infection. It is contemplated that these findings could be employed to facilitate post-translational silencing at the level of protein (e.g., removal of existing proteins), thus serving as a protein analog to CRISPR / Cas9 and RNAi / RISC, and further to enable sequence-specific silencing of host functions without the modification of the host genome.

The invention relates to an improved sample preparation method for LC-MS / MS analysis that enables an efficient isolation, purification and identification of protein contaminants, such as host cell proteins (HCPs) as process-related impurities generated during the production of biopharmaceuticals, such as monoclonal antibodies (mAbs).

The invention provides application of 7, 8-dihydroxyflavone in preparation of a medicine for treating diseases caused by herpes virus infection, and belongs to the technical field of biological medicine. The 7, 8-dihydroxy flavone can be used for remarkably inhibiting infection of herpes simplex viruses HSV-1 and HSV-2, and has broad-spectrum anti-HSV activity. According to the present invention, the HSV virus protein expression can be significantly inhibited by pretreating the virus with the 1, 7, 8-dihydroxyflavone and treating the cells after the virus adsorption, the virus plaque formation can be reduced, and the dose dependence can be provided; experiments show that the 7, 8-dihydroxyflavone plays the anti-herpes simplex virus activity mainly through targeting host protein fructose-diphosphate aldolase A. The 7, 8-dihydroxyflavone has the anti-herpes simplex virus activity. Mouse in-vivo experiments prove that the 7, 8-dihydroxyflavone can significantly improve the survival rate of HSV-1 mice, improve the weight reduction trend and reduce the virus titer of lung tissues; meanwhile, mouse genital organ lesions caused by HSV-2 infection can be remarkably relieved, and the weight of infected mice is improved. Therefore, the compound 7, 8-dihydroxyflavone is expected to be developed into a candidate drug for treating the herpes simplex virus.

The invention discloses a targeted nutrient source mining method based on beef cattle intestinal type-host gene interaction, particularly relates to the field of biological information data processing, and is used for solving the problems that existing nutrient source development lacks molecular mechanism verification and is poor in targeting. The method comprises the following steps: firstly, dividing nutrition-associated intestinal types based on microbiome and transcriptome data, and constructing a co-expression network to screen host co-expression specific genes driven by the specific intestinal types; then, establishing a flora metabolite ligand set and host protein receptor model, executing molecular conformation search and Gibbs free energy calculation, and screening high-activity targeting effect factors based on physical affinity; and finally, traversal matching and quantitative screening are carried out on the natural raw material liquid chromatography-mass spectrometry data by using the targeted effect factors, and a targeted nutrition source recommendation list aiming at the specific intestine type is generated. According to the method, multi-omics correlation analysis and molecular thermodynamics verification are fused, and an accurate development closed loop from micromechanism analysis to macroscopic raw material matching is constructed.

The invention belongs to the technical field of biology, and particularly relates to application of CD14 gene / protein as a target spot to screening of drugs for preventing or treating African swine fever virus infection, the inventor uses host protein CD14 as a research object to explore the influence of the host protein CD14 on ASFV infected host cells, and research results show that the CD14 protein can promote adsorption, internalization and replication of ASFV, and the CD14 gene / protein can be used for preparing drugs for preventing or treating ASFV infection. The siRNA, the antibody and the recombinant protein of the CD14 can inhibit ASFV infected cells, and vaccines or drugs for preventing or treating African swine fever virus infection can be screened or anti-African swine fever CD14 knockout pigs can be screened by taking the CD14 gene / protein as a target spot. The invention enriches the cognition of the host protein for regulating and controlling ASFV infection, provides theoretical support for the research and development of safe and effective ASF vaccines, and has important significance for the clinical treatment and prevention and control of African swine fever.

The invention provides a chicken FSHR (follicle stimulating hormone receptor) polyclonal antibody as well as a preparation method and application thereof. A prokaryotic expression target sequence of the chicken FSHR polyclonal antibody is as shown in SEQ ID NO: 1. The preparation method of the chicken FSHR polyclonal antibody is the preparation method of the chicken FSHR polyclonal antibody, and comprises the following steps: (1) recombining an FSHR gene into a prokaryotic expression vector, constructing a prokaryotic recombinant expression plasmid, transforming the prokaryotic recombinant expression plasmid into a host cell, performing induced expression, and purifying host protein; and (2) animal immunization, blood collection, serum separation, purification and titer determination. The polyclonal antibody can effectively recognize the endogenous chicken FSHR antigen and the FSHR protein expressed in chicken tissues, has high specific recognition capability, and lays a foundation for researching the structure and function of the chicken FSHR protein.

The invention discloses a nucleic acid molecule for inhibiting Zika virus, a pharmaceutical composition containing the nucleic acid molecule and application. The invention develops an anti-virus strategy for realizing the target host protein based on the RNA structure by changing the bottom-layer anti-virus logic. The MSI1 binding site in the nucleic acid molecule is highly conserved in all Zika virus strains, and the nucleic acid molecule has wide applicability. Meanwhile, the nucleic acid molecule can target an MSI1 high-expression region (namely virus-susceptible tissue), the problem of poor tissue specificity in existing delivery is solved, and the nucleic acid molecule is higher in targeting property, so that the nucleic acid molecule can cope with nervous system infection and pregnancy infection. In addition, the sequence design is relatively simple, and based on natural RNA sequence optimization, the modification demand is reduced, the natural affinity is high, and the chemical modification dependence is greatly reduced.

The invention discloses application of carfilzomib in preparation of a medicine for preventing and treating Nipah virus, and belongs to the technical field of medicine. The method mainly aims at ubiquitination modification of nipah virus M protein, the carfilzomib is used for inhibiting a host proteasome path, free ubiquitination factors in cells are depleted to achieve the effect of inhibiting ubiquitination of the M protein, then nucleoplasm shuttle of the M protein is inhibited, replication of the nipah virus is inhibited, and the effect is good. At present, most of research and development of virus medicines and vaccines are designed or modified aiming at viruses, a new thought is provided for research and development of medicines and vaccines in the future, and a new application is also provided for Carfilzomib.

The invention discloses an affinity purification process for human serum albumin and a DARPin dimer ligand, the DARPin dimer comprises a first DARPin monomer and a second DARPin monomer, and the first DARPin monomer and the second DARPin monomer both have a four-segment structure of N-cap, IR1, IR2 and C-cap; the amino acid sequences of the first DARPin monomer and the second DARPin monomer are selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4 or SEQ ID NO: 5 in a sequence list; the amino acid sequences of the first DARPin monomer and the second DARPin monomer have at least 90%-98% sequence identity with any one amino acid sequence selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4 or SEQ ID NO: 5, and maintain specific binding activity to human serum albumin. According to the present invention, through the N-cap, IR1, IR2 and C-cap four-segment type DARPin dimer design, the convection column matrix is optimized so as to obtain the novel ligand with high affinity and high specificity on the human serum albumin, and the non-specificity of the host protein and the similar structure impurities is significantly reduced;

The invention belongs to the field of biotechnology, and specifically relates to a method for introducing an early stop codon at a specific amino acid residue of a foot-and-mouth disease virus VP1 protein based on a genetic codon expansion technology, and using a biological orthogonal translation system to read through an amber stop codon UAG. Under the condition of the presence or absence of a non-natural amino acid, not only can the expression of the VP1 protein be conditionally controlled, and the non-natural amino acid can be introduced into the foot-and-mouth disease virus VP1 protein at a specific point, but also the foot-and-mouth disease virus VP1 protein can be specifically labeled with a non-natural amino acid containing a special group, and a stable covalent bond can be formed between proteins that interact with cells through light cross-linking, thereby providing a powerful means for studying the interaction between the foot-and-mouth disease virus and host proteins; and the method can also be used to prepare a replication-deficient recombinant foot-and-mouth disease virus and a vaccine with a mutation at a specific site of the VP1 protein.

Disclosed is a pharmaceutical composition to prevent transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pharmaceutical composition comprising: genetically modified bacteria; sequences of small peptides; and pharmaceutical excipients, wherein the genetically modified oral bacteria are modified to translate, produce, and emit the sequences of small peptides which neutralize SARS-CoV-2 against COVID-19, wherein transgenic technology is used to modify the genetically modified oral bacteria to add genes in genetically modified oral bacteria that are transcribed to produce small peptides from the sequences of small peptides so added, wherein the sequences of small peptides show extreme binding and neutralization to SARS-CoV-2 but not to host proteins or processes, and wherein the pharmaceutical excipients aid the oral and / or nasal administration of the pharmaceutical composition.

Provided herein is a synthetic polypeptide derived from a high mobility group cassette 1 (HMGB1) host protein that can both disrupt bacterial biofilm and prevent the formation of neutrophil extracellular traps (NETs). Also provided herein are methods of disrupting abnormal or excessive NET formation, which are particularly suitable for treating high risk populations, the composition can be used for people suffering from infection of SARS CoV-2, septicemia, autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, type I diabetes mellitus and small vasculitis), autoinflammatory diseases (such as gout and inflammatory bowel disease) and metabolic diseases (such as type 2 diabetes mellitus and obesity).

Dengue virus (DENV) is a mosquito-borne flavivirus responsible for dengue fever. Studies have shown that DENV interacts with metabolic pathways, in particular the glycolysis is increased in DENV-infected cells. However, the dependence of DENV on this pathway has not been investigated in details. The inventors identified an interaction between the non-structural protein 3 (NS3) of DENV and GCKR, a host protein that regulates the liver-specific hexokinase GCK. NS3 expression alone was found to increase glucose consumption and lactate secretion in an hepatic cell line expressing GCK. The inventors observed that GCKR interaction with GCK decreases DENV replication, supporting the role of NS3 as an inhibitor of GCKR function. By targeting NAD(H) biosynthesis with the antimetabolite 6-Amino-Nicotinamide (6-AN), the inventors decreased cellular glycolytic activity and inhibited DENV replication in hepatic cell. The present invention thus relates to the use of inhibitors of NAD biosynthesis for the treatment of dengue virus infections.

The invention discloses a host protein BRAP peptide fragment and application of the host protein BRAP peptide fragment in research and treatment of coronavirus, and particularly relates to identification of the BRAP peptide fragment having specific interaction with an SARS-CoV-2CoV-Y structural domain, development of a method for in-vitro identification of interaction of the peptide fragment and the coronavirus, preparation of drugs for inhibiting SARS-CoV-2 induced host inflammatory response by using the peptide fragment, and application of the host protein BRAP peptide fragment in research and treatment of the coronavirus. According to the method, a model for screening anti-SARS-CoV-2 drugs is constructed, and an in-vitro model for researching an SARS-CoV-2 infection mechanism is established, so that a theoretical basis and technical support are provided for deeply understanding the pathogenic mechanism of coronavirus and developing new antiviral drugs and treatment strategies. The peptide fragment interacts with a CoV-Y structural domain, the dissociation constant Kd of the interaction is 12.67 + / -0.2 mu M, and the stoichiometric ratio is 1: 1.

The application discloses a kind of multilocular hydatid Em Preparation method of 6B protein and application thereof in preparation of anti-host inflammatory response preparation. By protein structure modeling, molecular docking technology, it is confirmed that Em 6B can be combined with host 26S proteasome key subunit with high affinity, affect the assembly of host proteasome in vivo, and then intervene the activity of NF-κB signal pathway, so as to regulate host inflammatory response. Through animal experiment, it is shown that recombinant Em 6B intervention can significantly alleviate the colon injury of inflammatory bowel disease mice, regulate the expression level of pro-inflammatory and anti-inflammatory factors, and improve the survival rate of sepsis mice, and no obvious toxic side effects are observed. The application opens up a new path for developing anti-inflammatory preparations using parasite-host immune interaction natural molecules, and provides a kind of anti-host inflammatory response biological preparation technical scheme with novel mechanism of action and good biological safety, which has good application potential in the prevention and treatment of human and livestock inflammatory diseases.

The invention discloses a method for separating and purifying recombinant protein A with high loading capacity on a large scale, and provides a method for separating and purifying the recombinant protein A by using nickel ion chelation chromatography and anion exchange chromatography, the loading capacity of a nickel ion chelation chromatography sample is 40g / L, and the loading capacity of an anion exchange chromatography sample is 80g / L. According to the method, endotoxin and escherichia coli host protein are effectively removed, the purity of a recombinant protein A solution obtained through separation and purification is larger than 98% through HPLC and SDS-PAGE electrophoretic analysis, the endotoxin is smaller than 1 EU / mg, and the recovery rate is larger than 85%. The protein loading capacity is high, the technological process is simple, the cost is low, the applicability is wide, the purity and the recovery rate are high, meanwhile, the endotoxin control effect is remarkable, and therefore the protein A can be used as a raw material of immunoaffinity chromatography filler and is suitable for industrial production of recombinant protein A.

This invention discloses a multilocular echinococcosis larva. In Preparation method of -6B protein and its application in the preparation of anti-host inflammatory agents. Through protein structure modeling and molecular docking technology, the preparation method was confirmed. In -6B can bind with high affinity to a key subunit of the host 26S proteasome, affecting the assembly of the proteasome in the host and thus interfering with the activity of the NF-κB signaling pathway, thereby regulating the host inflammatory response. Animal experiments have shown that recombinant... In -6B intervention significantly alleviated colonic damage in mice with inflammatory bowel disease, regulated the expression levels of pro-inflammatory and anti-inflammatory factors, and improved the survival rate of septic mice, with no obvious toxic side effects observed. This invention opens up a new pathway for developing anti-inflammatory agents using natural molecules that interact with the parasite's immune system, and provides a novel mechanism of action and biosafety for anti-host inflammatory biological agents, showing great potential for application in the prevention and treatment of inflammatory diseases in humans and livestock.

Pathogens developing resistance to available drugs are of main concern in various diseases, including cryptococcosis and tuberculosis. Hence there is a need for therapeutics with novel mechanisms of action. Described herein are compositions and methods for treating infections (e.g., fungal infections) caused by microbes (e.g., fungi) comprising inteins. An intein is a moving protein element inside a host protein. Splicing off intein from the host protein is required to maturate and activate the host protein. Calcimycin (CMN) is used as an intein splicing inhibitor to block intein splicing of the Prp8 protein of fungal pathogen C. neoformans and C. gattii the causative agents of cryptococcosis, to treat patients.

This invention provides rice OsLHCA3 The uses of genes and their application in breeding virus-resistant rice, the above OsLHCA3 The nucleotide sequence of the gene is shown in SEQ ID NO.1. This invention utilizes transgenic technology to achieve overexpression in rice. OsLHCA3 This gene can significantly enhance rice's resistance to RSV. The mechanism lies in... OsLHCA3 The protein recruits the RSV motility protein NSvc4 to chloroplasts, interfering with the interaction between NSvc4 and the host protein OsREM1.4, thereby inhibiting the intercellular motility function of NSvc4. This invention provides a new gene resource for RSV-resistant rice breeding and has important application prospects.

The invention belongs to the technical field of molecular biology and immunology, and provides a host protein for inhibiting porcine epidemic diarrhea virus replication. The purpose of inhibiting the porcine epidemic diarrhea virus is achieved by screening medicaments capable of promoting Nox4 expression or improving protein activity, or the purpose of obtaining the Nox4 inhibitor is achieved by screening medicaments capable of inhibiting Nox4 expression or protein activity. Host cells with Nox4 genes knocked out or host cells in a Nox4 inhibitor environment are infected by porcine epidemic diarrhea viruses, so that the antigen of the inactivated vaccine is produced. The invention provides a new target for prevention and control of the porcine epidemic diarrhea virus, can be applied to virus-host interaction theory research of the porcine epidemic diarrhea virus and drug production of the porcine epidemic diarrhea virus, and has important significance in research and development of new drugs and vaccines.

The invention relates to the technical field of biology, and discloses an antiviral polypeptide and application thereof. According to the antiviral polypeptide provided by the invention, the host protein ARF4 is innovatively taken as a target spot, the purpose of resisting virus infection or relieving pathological lesions caused by virus infection is achieved by adjusting the function of the host protein, and the antiviral polypeptide has an excellent antiviral effect. The host protein is selected as a target spot, so that the antiviral polypeptide provided by the invention can well avoid the problem of vaccine or antiviral drug failure caused by strong RNA virus variability, and has higher stability and wider application prospect.