29 results about "Host factor" patented technology

This invention discloses the application of the DNAL1 gene as a target in screening drugs for the prevention and treatment of Zika virus or dengue virus type 2 infection, specifically the application of screening drugs for the prevention and / or treatment of Zika virus or dengue virus type 2 infection with the aim of inhibiting or knocking out the DNAL1 gene. The invention has found that the DNAL1 gene is a key host factor promoting the replication of Zika virus or dengue virus type 2, and that inhibiting the DNAL1 gene through siRNA or knocking out the DNAL1 gene through CRISPR / Cas9 can inhibit the replication of Zika virus or dengue virus type 2. The DNAL1 gene is a potential host factor for flaviviruses, and this invention provides a potential target for the prevention and / or treatment of Zika virus or dengue virus type 2 infection.

This invention relates to the field of gene editing, and in particular to a very small CRISPR / Cas12hacker gene cutting system. The CRISPR / Cas12 gene cutting system includes a Cas12hacker nuclease or a polynucleotide encoding the Cas12hacker nuclease, and also includes guide RNA or a polynucleotide encoding the guide RNA. By binding to the host factor thioredoxin TrxA, the CRISPR-Cas12 gene cutting system enhances the efficiency of the Cas12hacker nuclease in precisely cutting double-stranded DNA, thereby achieving genomic DNA double-strand breaks and highly efficient in vitro DNA double-strand cutting.

The invention belongs to the field of gene engineering, and particularly relates to establishment of an ALKBH5 gene knockout cell line and application of the ALKBH5 gene knockout cell line as a foot-and-mouth disease virus vaccine production cell line. According to the invention, firstly, the ALKBH5 gene knockout BHK-21 cell line is successfully constructed by using a CRISPR / Cas9 technology, after ALKBH5 is knocked out, the cell activity is not obviously influenced, but the replication of FMDV can be obviously promoted, and the ALKBH5 gene knockout BHK-21 cell line can be used as a production cell line of a foot and mouth disease virus vaccine; and secondly, by constructing an ALKBH5 wild type and an R131 site mutation plasmid and carrying out a back-up experiment, the result shows that the ALKBH5 can inhibit the replication of the FMDV. The invention discloses the negative regulation effect of ALKBH5 as a host factor on FMDV replication for the first time, and lays an important theoretical foundation for deep analysis of a molecular mechanism of ALKBH5.

The invention provides an antiviral drug screening marker and application of a microsome triglyceride transfer protein inhibitor in preparation of an antiviral drug, and finds new application of the microsome triglyceride transfer protein inhibitor in antiviral infection for the first time compared with the prior art. Experiments prove that the expression level of the microsome triglyceride transfer protein in the process of infecting cells with vesicular stomatitis virus is remarkably increased, and the microsome triglyceride transfer protein is used as an antiviral drug screening marker. The invention provides a new target spot for the treatment of virus infection, and the lomitapide as a marketed drug has verified safety, can be quickly transformed and applied, and has a wide application prospect. The invention has broad spectrum potential of targeting host factors or being effective to various viruses (such as coronavirus and influenza virus).

The invention discloses application of a nifU2 gene in inhibition of plant cell ferroptosis, and belongs to the technical field of gene engineering. The invention provides an effect of a plant iron-sulfur cluster transporter nifU2 in regulation and control of plant iron-sulfur clusters, and solves the problem of the effect of the plant iron-sulfur cluster transporter in ferroptosis in the prior art. The nifU2 participates in the process of plant ferroptosis, and participates in plant antiviral response by inhibiting ferroptosis. According to the application, nifU2 is identified as a regulatory factor of ferroptosis in plant cells for the first time, and subsequent exploration of ferroptosis related host factors and regulatory mechanisms thereof under other biological stress conditions is facilitated.

The invention discloses an application of a host factor HOXD1 in regulation and control of hepatitis B virus transcription. The research finds that HOXD1 interacts with HBx protein, so that the transcriptional activity of HBV is effectively inhibited; hBV replication can be promoted by knocking down HOXD1 expression, HBV transcription is remarkably inhibited by overexpressing HOXD1, and it is proved that the HOXD1 has a negative regulation function on virus replication; hOXD1 can be used as a potential anti-HBV drug target and is used for developing new drugs and new strategies for treating hepatitis B.

This invention relates to the fields of transcription factor engineering and metabolic engineering, and discloses an engineered strain that produces L-isoleucine, its construction method, and its applications. This strain... E. coli K12, MG1655 ( E. coli A1) serves as the host, integrating the subunit of the host factor IHF. ihfβ, ihfα Natural promoter replaced with P trc Strong promoters enable IHF overexpression, resulting in engineered bacteria. E. coli IHF4. This invention also discloses the construction steps of this strain, as well as its application method for L-isoleucine production by inoculating it into a fermentation medium, culturing it at 36-38℃ and 200 r / min for 40-60 h, and adjusting the pH and supplementing sugar. This engineered strain increases the yield of L-isoleucine by 42.11% compared to the starting strain. The construction method is simple and suitable for industrial microbial fermentation production of L-isoleucine.

The invention discloses an application of a small molecule drug ATWLPPR Peptide TFA in resisting mycobacterium bovis infection, and belongs to the field of biological medicine, the small molecule drug ATWLPPR Peptide TFA is an agonist of a target host factor NRP1, and then the inhibition effect of the ATWLPPR Peptide TFA on mycobacterium bovis in vitro and in vivo is researched. An in-vitro bacterial loading titration result shows that the ATWLPPR Peptide TFA treatment can present dose-dependent inhibition of the mycobacterium bovis to adhere to A549 cells. Mouse experiment results show that ATWLPPR Peptide TFA treatment can inhibit mice from being infected with mycobacterium bovis, pathological injuries of mouse lung tissues are effectively relieved, and a brand new direction is provided for prevention and control of mycobacterium bovis.

The invention relates to the technical field of biomedicine, in particular to a novel target spot for resisting chikungunya virus infection and application. According to the invention, human neuroblastoma cells (SH-SY5Y) and human brain astroblastoma cells (U87) are taken as target cells, and the expression of the target cell part capable of exerting receptor action membrane protein is down-regulated by adopting an RNA interference technology, so that a host factor capable of effectively inhibiting CHIKV infection of human nerve cells is found, and the purpose of blocking CHIKV infection from the source is achieved. It is found that platelet membrane glycoprotein VI (GP6) plays an important role in CHIKV infection SH-SY5Y and U87 cells, expression of GP6 is reduced, and CHIKV infection can be obviously inhibited. The invention provides an application of GP6 in preparation of a medicine for preventing or treating chikungunya virus infection, and provides a new target spot and a treatment scheme for clinically preventing and treating fever, arthralgia, joint swelling, muscle pain, headache, nausea, fatigue, rash and other diseases caused by CHIKV infection.

The invention belongs to the technical field of medicines, and discloses application of IRE1alpha protein or a coding gene thereof as a new target spot for treating hepatitis B virus. The invention reveals for the first time that IRE1alpha protein weakens the recruitment and function of HBV specific CD8 + T cells by promoting macrophages to be polarized to anti-inflammatory phenotypes and inhibiting secretion of chemotactic factors CCL5, and the IRE1alpha protein is a key host factor for maintaining immune tolerance. On the basis, the invention provides an application of a small-molecule inhibitor targeting IRE1alpha in resisting HBV, and provides a new molecular mechanism and a candidate drug for functional healing of HBV.

The invention provides a novel isoxazolopyrimidine derivative, a pharmaceutical composition and application of the novel isoxazolopyrimidine derivative, and belongs to the technical field of medicine synthesis. The novel isoxazolopyrimidine derivative provided by the invention can be used in drugs for inhibiting human immunodeficiency virus activity. The targeted drug inhibits interaction between the virus capsid protein and the host factor CPSF6, prevents nuclear input in HIV-1 virus infection and a transcriptional activation region positioning process, and achieves an efficient antiviral effect.

The invention discloses a transcriptional activation type RUBY visual virus infection system as well as a method and application thereof. The system is based on a betacyanin biosynthesis pathway, a transcriptional activation system is utilized, and a yeast GAL4 DNA binding domain (BD) and a herpes virus VP16 transcriptional activation domain (AD) are fused and constructed in a virus vector; when the virus infects expressed transgenic tobacco, the expression of the RUBY whole gene can be activated, so that a red signal is generated. The construction method of the system is clear, complex instruments are not needed, an efficient and convenient tool platform is provided for protein function analysis, host factor screening and infection mechanism exploration in virology research, and good expandability is achieved.

This invention relates to the field of biotechnology, specifically to a method for elucidating the interaction complex between the BTVNS2 protein and host cells. The method involves constructing an initial list of host proteins through cross-validation using affinity purification-mass spectrometry and biotinylate proximity labeling-mass spectrometry. Weighted scoring and ranking are then performed based on quantitative mass spectrometry data and functional relevance. Binding characteristics are validated and quantified intracellularly and extracellularly using immunoprecipitation and biophysical techniques, respectively. The complex is assembled in vitro, and its high-resolution three-dimensional structure is resolved using single-particle cryo-electron microscopy. This invention addresses key problems in existing technologies, such as incomplete capture of interacting proteins, high false-positive rates, blind functional screening, and difficulty in obtaining samples suitable for high-resolution structural analysis due to reliance on single methods. It systematically identifies key host factors and ultimately reveals the precise structure of the interaction interface at the atomic level, providing a foundation for understanding viral replication mechanisms and developing antiviral strategies.

This invention discloses the application of host ITCH as a drug target in the preparation of drugs against normal flavivirus infection, belonging to the field of biomedical technology. This invention is the first to propose and verify the host E3 ubiquitin ligase ITCH as a key target for anti-normal flavivirus infection, and provides an antiviral strategy based on interfering with the interaction between host ITCH and normal flavivirus capsid proteins or inhibiting the expression level / ubiquitin ligase activity of host ITCH. Unlike existing mainstream viral target strategies, this invention is a novel antiviral approach based on host factors, providing a new target and theoretical basis for developing broad-spectrum, low-drug-resistance anti-normal flavivirus drugs.

The invention discloses an application of an eIF2alpha kinase regulator in preparation of an anti-coronavirus drug. The invention provides an application of an eIF2 alpha kinase regulator in preparation of an anti-coronavirus drug. The coronavirus is an alpha coronavirus, a beta coronavirus, a gamma coronavirus or a delta coronavirus. The invention focuses on antiviral host factors, provides a target compound for targeting host eIF2alpha kinase, eIF2alpha phosphorylation and protein synthesis, plays an antiviral role by accurately regulating and controlling host virus interaction, and is beneficial to overcoming virus resistance and obtaining broad-spectrum antiviral activity.

The invention relates to the technical field of biomedicine, in particular to a novel target spot for resisting chikungunya virus infection and application. According to the invention, human neuroblastoma cells (SH-SY5Y) and human brain astroblastoma cells (U87) are taken as target cells, and the expression of the target cell part capable of exerting receptor action membrane protein is down-regulated by adopting an RNA interference technology, so that a host factor capable of effectively inhibiting CHIKV infection of human nerve cells is found, and the purpose of blocking CHIKV infection from the source is achieved. The invention discovers that the nerve cilia protein 2 (NRP2) plays an important role in CHIKV infection SH-SY5Y and U87 cells, and the CHIKV infection can be obviously inhibited by down-regulating the expression of the NRP2. The invention provides an application of NRP2 in preparation of a medicine for preventing or treating chikungunya virus infection, and provides a new target spot and a treatment scheme for clinically preventing and treating fever, arthralgia, arthrocele, muscular pain, headache, nausea, fatigue, rash and other diseases caused by CHIKV infection.

The present invention provides live attenuated vaccines for the prophylactic treatment of Chikungunya virus infections. The vaccines comprise a genetically modified Chikungunya virus that has a reduced replication capacity due to a mutation or deletion in the R5 region of the hypervariable domain of nsP3, a nonstructural protein that interacts with host factors. The inventors have indeed discovered that the R5 region of the hypervariable domain of nsP3, a nonstructural protein that interacts with host factors, is critical for CHIKV replication and pathogenesis. Specifically, the inventors have shown that the R5 region is required for the interaction of nsP3 with FHL1, BIN1 and CD2AP, three host proteins that are involved in the regulation of actin cytoskeleton and membrane trafficking. These host proteins are expressed in muscle and joint tissues, which are the main targets of CHIKV infection and inflammation. By mutating or deleting the R5 region of nsP3, the inventors have generated a genetically modified CHIKV (CHIKV-ΔR5) that has a reduced replication capacity and virulence compared to the WT virus. Moreover, the inventors have demonstrated that CHIKV-ΔR5 is able to elicit a strong neutralizing antibody response and protect mice from lethal challenge with WT virus. The present invention also provides screening methods for identifying test substances that are capable of inhibiting the interaction between nsP3 and FHL1, CD2AP and BIN1, wherein the selected test substances would be suitable for the treatment of CHIKV infections.

The invention discloses a separated RUBY visual virus infection system as well as a construction method and application thereof. According to the system, a key gene of a betacyanin biosynthetic pathway is split into two parts: CYP76AD1 and a GT gene are connected in series through a 2A peptide sequence and are constructed in a plant stable expression vector, and a stably inherited transgenic plant is obtained in nicotiana benthamiana; and cloning another key gene DODA into a plant virus vector to construct a recombinant virus expression vector. According to the method, real-time, lossless and in-situ visual observation of the virus infection and movement process is achieved, the system construction method is clear, complex instruments are not needed, an efficient and convenient tool platform is provided for protein function analysis, host factor screening and infection mechanism exploration in virology research, and good expandability is achieved.

The application provides an antiviral drug screening marker and an application of a microsomal triglyceride transfer protein inhibitor in preparation of an antiviral drug, and compared with the prior art, the application firstly finds a new use of the microsomal triglyceride transfer protein inhibitor in antiviral infection. The application proves by experiments that the expression level of the microsomal triglyceride transfer protein is significantly increased in the process of vesicular stomatitis virus infection of cells, and the microsomal triglyceride transfer protein is used as an antiviral drug screening marker. The application provides a new target for treatment of viral infection, and lomitapide is an already-marketed drug, the safety of which has been verified, can be quickly converted for application, and has wide application prospect. Moreover, the application has broad-spectrum potential: targeting a host factor, or being effective for multiple viruses (such as a coronavirus and an influenza virus).

An anti-HBV agent according to the present invention contains, as an active ingredient, a substance which binds to LIPG and inhibits the functions of LIPG. The inventors of the present application have found that LIPG is a factor that plays an important role in the adhesion and uptake of HBV, and has a function as a cofactor, which supports the intracellular invasion of HBV independently of NTCP, and also contributes to the proliferation of HBV in cells. The LIPG-binding substance exhibits an anti-HBV action by: binding, when on the surface of hepatocytes, to LIPG to inhibit the cell adhesion and uptake of HBV; and binding, when delivered into the hepatocytes, to LIPG present in cells to inhibit any step in the intracellular proliferation of HBV.

This invention discloses the application of the silkworm TUSC3 gene in the prevention and control of silkworm nucleopolyhedrovirus (BmNPV) infection. This invention is the first to discover that the silkworm TUSC3 gene is a key host factor upon which BmNPV replication depends. Through NGI-1 inhibitor treatment, siRNA interference, and overexpression experiments, the crucial role of TUSC3 in BmNPV proliferation was systematically demonstrated at three levels: drug inhibition, gene knockdown, and gene overexpression. Targeting the TUSC3 gene or its encoded protein using RNA interference technology, small molecule inhibitors, or gene editing effectively inhibits BmNPV proliferation. Through gene editing breeding technology, transgenic antiviral silkworm lines with TUSC3 function loss or downregulated expression were cultivated. This invention not only provides a new perspective for elucidating the molecular mechanism of the interaction between silkworm and BmNPV, but also provides important technical support and germplasm resources for developing new antiviral strategies based on host factors.

The invention discloses an application of a host factor TMEM40 in regulation and control of hepatitis B virus antigen expression and HBV resistance. According to the invention, a series of novel host factors for regulating and controlling HBsAg expression are identified by utilizing a protein spectrum, and by screening the host factors, the TMEM40 shows a strong inhibition effect on hepatitis B virus surface antigens in a cell model, and the effect of the TMEM40 gene in inhibiting hepatitis B virus is provided for the first time. Researches show that TMEM40 is expected to be used for developing a novel therapeutic drug for inhibiting hepatitis B virus surface antigen, and a new strategy is provided for HBV functional cure.

The invention discloses an application of a DNAL1 gene as a target spot in screening of drugs for preventing and treating Zika virus or type 2 dengue virus infection, namely an application of screening of drugs for preventing and / or treating Zika virus or type 2 dengue virus infection with the purpose of inhibiting expression of the DNAL1 gene or knocking out the DNAL1 gene. The research finds that the DNAL1 gene is a key host factor for promoting the replication of the Zika virus or the dengue virus type 2, and the replication of the Zika virus or the dengue virus type 2 can be inhibited through siRNA inhibition or CRISPR / Cas9 knockout of the DNAL1 gene; the DNAL1 gene is a potential flavivirus host factor, and a potential target is provided for prevention and / or treatment of Zika virus or type 2 dengue virus infection.

This invention belongs to the fields of genetic engineering and fish molecular breeding technology, specifically relating to the application of ARMH3 inhibitors in the preparation of antiviral drugs for fish or the creation of hemorrhagic disease-resistant fish germplasm. This invention discloses that ARMH3 is an important host factor for grass carp reovirus infection. The amino acid sequence of ARMH3 is shown in SEQ ID NO.1. ARMH3 is utilized by grass carp reovirus, promoting viral inclusion body formation, thereby facilitating viral replication and infection. This invention utilizes inhibitors of the ARMH3 protein encoded in grass carp... ARMH3 Genes were edited using CRISPR / Cas9 to create... ARMH3 Knockout chimeric grass carp populations exhibit significant resistance to hemorrhagic disease. This invention provides molecular targets and methods for the rapid creation of new grass carp germplasm resistant to hemorrhagic disease.

The invention discloses a virus replication essential protein gene NdelF4G and application thereof in inhibition of plant virus infection, and belongs to the technical field of plant molecular biology and virus resistance. The nucleotide sequence of the gene is as shown in SEQ ID NO: 3, and the coded amino acid sequence of the gene is as shown in SEQ ID NO: 4. According to the invention, the endogenous NhelF4G gene of tobacco is specifically silenced through a virus-induced gene silencing technology, so that the infection and accumulation of tomato spotted wilf virus and rice stripe virus in nicotiana benthamiana can be remarkably inhibited, and the infection and accumulation are shown as reduction of disease symptoms and reduction of virus protein expression level. The discovery shows that the NhelF4G is a key host factor on which virus replication depends, and the NhelF4G can effectively endow plants with antiviral ability when being used as a silence target. The invention provides important gene resources and theoretical basis for creating novel antiviral plant materials and developing broad-spectrum virus prevention and control strategies of targeted host factors.

The invention belongs to the technical field of genetic engineering and fish molecular breeding, and particularly relates to application of an ARMH3 inhibitor in preparation of fish antiviral drugs or creation of anti-hemorrhagic disease fish germplasm. The ARMH3 is an important host factor for grass carp reovirus infection, the amino acid sequence of the ARMH3 is as shown in SEQ ID NO.1, the ARMH3 is utilized by grass carp reovirus, and virus replication and infection are facilitated by promoting formation of virus inclusion bodies. The CRISPR / Cas9 gene editing is carried out on the ARMH3 gene for coding the ARMH3 protein in the grass carp, and the created ARMH3 knockout chimera grass carp population has the remarkable advantage of resisting the hemorrhagic disease. The invention provides a molecular target and a method for rapidly creating a novel germplasm of the hemorrhagic disease-resistant grass carp.

This invention relates to the field of disease treatment, specifically providing the use of AMBRA1 inhibitors in the preparation of medicaments for the prevention and / or treatment of influenza virus infection, as well as methods for screening drugs. AMBRA1 is involved in the replication of multiple types of influenza viruses, including seasonal influenza A and influenza B, as well as avian influenza H5N1, H5N6, and H9N2, and is a broad-spectrum influenza host factor, providing candidate drug targets for the development of broad-spectrum anti-influenza drugs.

The application belongs to the technical field of biotechnology, and particularly relates to a recombinant vector, a cell, a kit and a method for screening of a host factor dependent on influenza virus polymerase activity. The application provides a recombinant vector, which is configured with an mScarlet reporter gene through a double tandem strategy (PB1-PB2, PA-NP), and a red fluorescent cell line stably expressing H5N1 polymerase driven by the red fluorescent cell line can be efficiently constructed by using only three lentiviral vectors. Compared with a traditional co-transduction method of five vectors, the difficulty of multiple vectors entering the same cell is greatly reduced, and the recombinant vector does not need live virus and can be stably passaged for a long time. Based on the recombinant vector, a host factor affecting polymerase activity is screened by using a whole genome CRISPR under a non-infectious state, and the method has the advantages of simple operation, high throughput and low cost.

The invention provides a method for rapidly screening a Zika virus infection resistant kinase inhibitor and application. The method is used for identifying a host kinase target spot for regulating and controlling Zika virus (ZIKV) infection. Based on the obtained kinase target, a rapid verification and kinase inhibitor development platform is further established, and a new strategy is provided for research and development of anti-ZIKV drugs of targeted host factors. According to the kinase target, the key dependent host kinase replicated by ZIKV is systematically identified by constructing kinase specific sgRNA library cells A549 and combining high-throughput function screening. The method overcomes the limitation that a traditional virus targeted drug easily generates drug resistance, realizes efficient conversion from host target discovery to potential inhibitor development, and solves the key problems of low flux, long period and high false positive rate in the prior art.