47 results about "Host factor" patented technology

The invention belongs to the field of biological medicines, and discloses an application of a VPS35 inhibitor in preparation of Zika virus infection resistant drugs, the VPS35 inhibitor comprises at least one of the following two substances: I: a substance for inhibiting VPS35 gene expression in host cells; and II: a substance for inhibiting the retrograde transport function of the VPS35 protein in the host cell. The invention finds that the VPS35 protein is an important host factor of the replication period of the Zika virus for the first time, and a Zika virus infection model system verifies that the replication of the Zika virus in the host cell can be inhibited by inhibiting the expression of the VPS35 gene in the host cell or inhibiting the retrograde transport function of the VPS35 protein. Compared with traditional drugs targeting Zika virus protein, the VPS35 inhibitor provided by the invention targets host factors, is more difficult to induce Zika virus drug resistance, and has more lasting treatment potential.

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.

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 colon cancer cells (HCT116) are taken as target cells, and retinoic acid-induced protein expression of the target cells is reduced by adopting a gene knockout technology, so that host factors capable of effectively inhibiting CHIKV infection of the human colon cancer cells are found, and the purpose of blocking CHIKV infection from the source is achieved. It is found that retinoic acid induced protein 16 (RAI16) plays an important role in CHIKV infected HCT116 cells, and CHIKV infection can be obviously promoted by down-regulating expression of RAI16. The invention provides an application of RAI16 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 application discloses the use of TIAR inhibitors for treating hepatitis B virus infection. The present application demonstrates that the host factor TIAR promotes HBV replication by regulating the translation of pgRNA through its binding, i.e. inhibiting the translation of nucleocapsid protein but promoting the translation of Pol. It is also found that TIAR is also packaged into the nucleocapsid of HBV through its binding to pgRNA. The present application provides a new solution for treating HBV infection based on TIAR as a target by reducing the expression of TIAR or inhibiting the binding of TIAR to pgRNA to inhibit HBV replication.

This invention relates to the field of pharmaceutical technology, specifically the application of NEDD8 activator in the preparation of drugs for treating Japanese encephalitis. Using human neuroblastoma cells (SH-SY5Y) as target cells, this invention utilizes activators from a library of ubiquitinated compounds to target and activate key enzymes in the ubiquitination pathway, aiming to identify host factors associated with Japanese encephalitis virus (JEV) infection of SH-SY5Y cells. This helps to understand the mechanism by which JEV invades the central nervous system and causes neuronal cell damage, and also provides new targets for therapeutic drugs against JEV-induced Japanese encephalitis. This invention experimentally discovered that NEDD8 activator (NAE) has the property of inhibiting JEV infection of SH-SY5Y cells. This invention provides the application of NEDD8 activator in the preparation of drugs for treating Japanese encephalitis, offering new targets and treatment strategies for the prevention and treatment of JEV.

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.

This invention relates to the field of pharmaceutical technology, specifically the application of NEDD8 activator enzyme inhibitors or their hydrochlorides in the preparation of drugs for treating Japanese encephalitis. This invention utilizes inhibitors from a library of ubiquitinated compounds to target and inhibit key enzymes in the ubiquitination pathway, aiming to identify host factors associated with Japanese encephalitis virus (JEV) infection of SH-SY5Y cells. This contributes to understanding the mechanism by which JEV invades the central nervous system and causes neuronal cell damage, and also provides new targets for therapeutic drugs against JEV-induced Japanese encephalitis. This invention discovers that NEDD8 activator enzyme (NAE) inhibitors or their hydrochlorides possess the property of inhibiting JEV infection of SH-SY5Y cells. This invention provides the application of NEDD8 activator enzyme inhibitors or their hydrochlorides in the preparation of drugs for treating Japanese encephalitis, offering new targets and therapeutic strategies for the prevention and treatment of JEV.

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 discloses an application of a small molecule drug TUG-1375 of a target host factor FFAR2 in resisting influenza virus infection, and belongs to the field of biomedicine.A plaque titration experiment is used for detecting the influence of the small molecule drug TUG-1375 on replication of different subtypes of influenza viruses after A549 cells are treated, it is found that the small molecule drug TUG-1375 has no influence on WSN (H1N1) and AH05 (H5N1) virus replication, and the small molecule drug TUG-1375 can be used for resisting influenza virus infection. However, replication of SH13 (H9N2) and FZ09 (H1N1) influenza viruses can be inhibited. Western blotting results show that the small molecule drug TUG-1375 inhibits influenza virus replication by inhibiting expression of FZ09 (H1N1) influenza A virus advanced protein M1, further tamps the host factor FFAR2 to play an important regulation function in regulation of influenza virus replication, can become an ideal drug target for resisting influenza virus replication, and has a potential application value.

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

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.

The invention discloses application of a host factor RAB10 in regulation and control of hepatitis B virus antigen expression and anti-hepatitis B virus. The invention provides an application of a host factor RAB10 or a coding gene thereof in regulation and control of hepatitis B virus replication or hepatitis B virus antigen expression level in host cells, and an application of the host factor RAB10 or an expression promoter thereof in preparation of drugs for resisting hepatitis B virus or inhibiting hepatitis B virus antigen. The invention also discloses application of the host factor RAB10 or the coding gene thereof as a drug target in screening drugs for resisting hepatitis B virus or inhibiting hepatitis B virus antigen. Researches show that RAB10 can significantly inhibit HBsAg expression, HBV DNA replication, HBV RNA transcription and HBs protein level, is expected to be used for developing a novel therapeutic drug for inhibiting hepatitis B virus surface antigen, and provides a new strategy for HBV functional cure.

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.

This invention relates to the field of pharmaceutical technology, specifically the application of deubiquitinase USP20 inhibitors in the preparation of drugs for treating Japanese encephalitis. This invention uses human neuroblastoma cells (SH-SY5Y) as target cells and utilizes inhibitors from a library of ubiquitination compounds to target and inhibit key enzymes in the ubiquitination pathway, aiming to identify host factors associated with Japanese encephalitis virus (JEV) infection of SH-SY5Y cells. This helps to understand the mechanism by which JEV invades the central nervous system and causes neuronal cell damage, and also provides new targets for therapeutic drugs against JEV-induced Japanese encephalitis. This invention experimentally demonstrated that deubiquitinase USP20 inhibitors have the property of inhibiting JEV infection of SH-SY5Y cells. This invention provides the application of deubiquitinase USP20 inhibitors in the preparation of drugs for treating Japanese encephalitis, offering new targets and treatment strategies for the prevention and treatment of JEV.

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 application belongs to the field of biological medicine, and relates to application of a CLIC1 inhibitor in preparation of an anti-zika virus infection drug, wherein the CLIC1 inhibitor comprises at least one of the following two substances: I: a substance for inhibiting expression of a CLIC1 gene in a host cell; II: a substance for inhibiting a CLIC1 chloride channel function in the host cell. The application first discloses that the CLIC1 gene and protein are key host factors for zika virus replication, and zika virus replication can be blocked by inhibiting the expression or chloride channel function, thereby providing a new direction for development of an anti-zika virus drug targeting a host. Compared with traditional drugs targeting zika virus proteins, the anti-zika virus infection drug prepared by using the CLIC1 inhibitor targets a host factor, is more difficult to induce virus drug resistance, and has more persistent treatment potential.

The present invention provides the use of higenamine in preventing and treating the novel coronavirus, belonging to the field of traditional Chinese medicine application technology. Higenamine can target host factors and, as an activator of host factors, inhibit the replication of the novel coronavirus. It has broad-spectrum antiviral activity and plays an important role in the prevention and treatment of the novel coronavirus. Compared with existing novel coronavirus treatment drugs, the compounds of the present invention have different antiviral mechanisms of action and are a beneficial supplement to existing antiviral drugs, providing a new option for antiviral treatment drugs.

The present invention discloses the application of the SNX19 gene in regulating the replication of porcine deltavirus, and belongs to the field of biotechnology. The present invention uses shRNA interference, overexpression, and the construction of an SNX19 knockout cell line in LLC-PK1 cells to confirm for the first time that knocking out the SNX19 gene or inhibiting the expression of the SNX19 gene can significantly inhibit the proliferation of PDCoV in host cells; overexpression of the SNX19 gene can promote the proliferation of PDCoV in host cells, indicating that SNX19 in host cells is an important host factor related to the proliferation of PDCoV and plays an important role in the development of cell vaccines. The improvement of viral proliferation efficiency can directly improve the economic benefits of vaccine manufacturers. On the other hand, using SNX19 as a drug target can further screen drugs that target and inhibit SNX19, and using it as a candidate drug can develop effective anti-porcine deltavirus drugs.

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.