94 results about "Pox viruses" patented technology

The invention belongs to the technical field of immunotherapy, and particularly relates to a monkey pox virus antigen epitope peptide and application thereof. The invention aims to solve the technical problem that at present, a T cell antigen epitope peptide for universal vaccines of monkey pox viruses is not developed in the field of monkey pox viruses. According to the technical scheme of the invention, the amino acid sequence of the monkey pox virus antigen epitope peptide is shown as SEQ ID No.2. The antigen epitope peptide provided by the invention has very strong immunogenicity, and can induce antigen-specific CD8 + T cells; the antibody can be directly loaded to antigen presenting cells, can activate T cells and effectively induce T cell immunity, and can be used for research and development and preparation of universal vaccines for monkey pox viruses, research and development of drugs and clinical treatment.

The invention discloses an SOD2 knockout cell line and application of the SOD2 knockout cell line in anti-poxvirus, and relates to the technical field of antiviral research. According to the invention, sgRNA of targeted superoxide dismutase 2 (SOD2) is designed, the sequence of the sgRNA is shown as SEQ ID NO.1-SEQ ID NO.2, then a stable SOD2 knockout human-derived non-small cell lung cancer A549 cell line is established by combining CRISPR / Cas9 gene editing with a lentiviral vector delivery technology, single-cell cloning is obtained through multiple rounds of puromycin screening, and the SOD2 gene knockout A549 cell strain is successfully constructed. Vaccinia virus Tian Tan strain infection shows that the number of plaques of SOD2 knockout cells is obviously greater than that of the plaques (about 2.3 times) of normal cell infection, and the plaques are relatively large, so that fine SOD2 has the effect of limiting intercellular transmission of poxvirus. The invention lays a foundation for research and preparation of antiviral drugs.

Therapeutic polypeptides, compositions thereof and methods of use thereof for activating NK cells and treating tumors are provided. The therapeutic polypeptides can include a first domain for binding NKG2D and a second domain for binding a tumor target.

The invention discloses a novel one-pot RPA-CRISPR method for detecting monkey pox virus based on a sucrose-assisted multiphase solution system, sucrose is added in RPA reaction to increase the density of the RPA reaction, the RPA reaction is placed at the bottom of a tube, and the CRISPR reaction with lower density is kept in a water phase and located at the top of the RPA reaction; in a one-tube reaction process, newly accumulated RPA amplicons trigger non-specific cutting of Cas12a for ssDNA-FQ, so that a fluorophore is released, a real-time fluorescence signal is detected by using a fluorescence detector, and end point fluorescence can be visualized under a blue light source; compared with the prior art, the one-pot RPA-CRISPR method of the multiphase solution system is constructed by using the sucrose to increase the RPA reaction density, rapid, convenient and reliable detection of the monkey pox virus is realized, prevention and control of the monkey pox epidemic situation are facilitated, and a good example is provided for actual field detection application of the sucrose-assisted multiphase solution system.

The present invention relates to a method for producing a poxvirus viral vector-based vaccine product from a avian cell line. In some embodiments, the avian cell line is a suspended quail cell line. Pharmaceutical compositions, such as vaccines, produced by the method of the present invention are also provided. In some embodiments, the poxvirus viral vector is modified vaccinia virus ankara ("MVA") or recombinant MVA. In some embodiments, the recombinant MVA encodes a heterologous antigen and can be used to produce a vaccine against that antigen. In some embodiments, the recombinant MVA encodes an antigen of respiratory syncytial virus (RSV), and the avian cell line is used to produce a vaccine against RSV containing recombinant MVA and / or the encoded antigen.

The invention relates to the technical field of medicines, in particular to application of aspiramycin and / or imiquimod in preparation of a medicine for treating VACV. Aspiramycin and imiquimod which are screened from medicines on the market have antiviral activity, and experimental data show that the Aspiramycin and the imiquimod have anti-VACV medicine activity. Aspiramycin and imiquimod (especially combined application) are used for preparing the medicine for treating VACV, so that the time and cost of preclinical research can be greatly reduced. As the action mechanism of the pox viruses is not unique to the VACV, the combined strategy has the potential to be expanded to infection treatment of other pox viruses (such as monkey pox virus MPXV) and even other DNA (Deoxyribose Nucleic Acid) viruses.

The invention discloses an application of diphyllin in preparation of drugs for inhibiting poxvirus and preventing or treating poxvirus infection, the poxvirus is common orthopoxvirus poxvirus, the poxvirus comprises vaccinia virus (VACV), vaccinia virus (CPXV) and rabbit poxvirus mucinoma virus (MYXV), the content of diphyllin is in a range of 1.25-2.5 [mu] M / mL, and the content of diphyllin is in a range of 1.25-2.5 [mu] M / mL. The compound has a remarkable inhibiting effect on infection of poxvirus family members such as CPXV, is expected to be used as a medicine for preventing and treating infection of CPXV and other poxviruses, and has important significance on prevention and control of diseases related to poxvirus infection.

The present application relates to a kind of recombinant vaccinia virus and its use, which is deleted at least one of TK gene, F4L gene and B2R gene relative to vaccinia virus Tianlu strain.The recombinant vaccinia virus of the present application has the characteristics of low toxicity, can be completely replicated and has higher immunogenicity.Therefore, the recombinant vaccinia virus provided by the present application has higher safety and enhanced immunogenicity.The recombinant vaccinia virus provided by the present application has higher application value as vaccine, can be used for preventing the infection of poxviridae virus, and as virus vector for constructing other infectious disease vaccine and tumor vaccine etc..

The invention belongs to the technical field of biology, and discloses an anti-monkey pox virus E8 antibody or an antigen binding fragment thereof and application thereof. The invention provides an anti-monkey pox virus E8 monoclonal antibody 2F6, 9G4, 9H1 or 10E11, which can specifically recognize and target orthopox viruses such as monkey pox, vaccinia and the like, and shows efficient virus neutralizing capacity. The clinical application value of preventing and treating orthopoxvirus infection is realized; the compound can be used for detecting orthopoxvirus, diagnosing diseases related to orthopoxvirus infection and preventing and / or treating orthopoxvirus infection and / or diseases related to orthopoxvirus infection.

The present invention generally relates to a method for designing recombinant poxviruses for therapeutic vaccines, i.e., personalized cancer vaccines, wherein the recombinant poxviruses comprise one or more expression cassettes, each expressing a fusion of multiple peptides (i.e., neopeptides), the method comprising performing, by a processing means (11) of a server (1), the following steps: (a) selecting a first subset of candidate peptides, wherein the candidate peptides exhibit a membrane-spanning score below a TMS threshold; (b) determining an optimal distribution of the candidate peptides from the first subset into one or more expression cassettes from among a plurality of possible distributions, wherein, if more than one expression cassette is present, the optimal distribution exhibits the lowest range of hydropathic scores of the two or more expression cassettes; (c) determining, for each expression cassette, an optimal slot assignment of the candidate peptides as a function of the cassette's slot occupancy rules, in order to select the peptide fusion with the lowest TM score; and (d) determining a DNA transfer sequence comprising the nucleotide sequence of the one or more expression cassettes to generate the recombinant poxvirus.

The invention provides a 2-deoxy-2-fluoro-beta-D-furan nucleoside derivative as well as a preparation method and application of the 2-deoxy-2-fluoro-beta-D-furan nucleoside derivative. The derivative has a structure as shown in I or II. The invention also relates to a preparation method of the compound and application of the compound as an anti-poxvirus inhibitor in preparation of anti-poxvirus drugs.

The present invention relates to recombinant poxvirus, such as recombinant Modified Vaccina Virus Ankara (MVA), encoding a fusion protein comprising a disease-associated antigen that is joined to a subunit of a self-assembling protein nanoparticle, and to medical uses thereof.

Provided are a poxvirus mRNA vaccine and a use. Specifically, provided is an isolated mRNA molecule, comprising a coding region, the coding region coding a target protein, and the target protein comprising the following four proteins: vaccinia virus surface antigens A27, L1, A33, and B5, wherein every two adjacent proteins are independently directly linked or linked by identical or different linkers. Animal immunization results show that the mRNA molecule has good candidate vaccine potential and provides an innovative idea for the development of poxvirus vaccines.

The present invention relates to monoclonal antibodies or antigen-binding portion thereof that have neutralizing or cross-neutralizing activity against poxvirus, in particular against monkeypox virus, vaccinia virus and cowpox virus. The invention relates also to the use of such monoclonal antibodies or antigen binding portion thereof in therapy, prophylaxis and diagnosis of poxvirus, in particular monkeypox virus, vaccinia virus and cowpox virus dependent diseases.

The present disclosure provides pharmaceutical compositions for delivery of orthopoxvirus antigens (e.g., mpox, variola, borealpox, ectromelia, cowpox, volepox, modified vaccinia virus Ankara, or vaccinia) and related technologies (e.g., components thereof and / or methods relating thereto). For example, the present disclosure provides polyribonucleotides encoding one or more mpox antigens, fragments, or fusions thereof.

The invention provides an anti-orthopoxvirus monoclonal antibody and application thereof, the monoclonal antibody is obtained by screening through a flow cytometry sorting technology and a single cell PCR technology, has a unique CDR partition, and is mainly used for recognizing L1R (M1R) antigen protein of orthopoxvirus. The affinity of the antibody to VARV (Vector Activated Receptor Virus), VACV (Vector Activated Receptor Virus), CPXV (Cytopoxvirus) and MPXV (Metapoxvirus) of orthopoxvirus is 1.84 nM, 1.46 nM, 2.71 nM and 2.57 nM respectively. In a virus neutralization experiment, the IC50 of the antibody and mature virions in vaccinia virus cells is 37.93 pM. In a monkey pox virus infected mouse model, the antibody can treat a monkey pox virus infected mouse. The monoclonal antibody disclosed by the invention has the characteristics of high expression, high neutralizing activity and good broad spectrum, can be used for industrial production, and can be applied to coping with orthopoxvirus infection outbreak possibly occurring in the future.

The present invention relates to methods of producing poxvirus viral vector-based vaccine products from avian cell lines. In some embodiments, the avian cells are suspension quail cell lines. Pharmaceutical compositions such as vaccines produced by the methods of the invention are also provided. In some embodiments, the poxvirus viral vector is Modified Vaccinia Virus Ankara (“MVA”) or recombinant MVA. In some embodiments, the recombinant MVA encodes heterologous antigens and can be used to produce a vaccine against the antigens. In some embodiments, the recombinant MVA encodes antigens of Respiratory Syncytial Virus (RSV) and the avian cells are used to produce a vaccine against RSV comprising the recombinant MVA and / or the encoded antigens.

The application provides application of Gidalizie in preparation of an anti-monkeypox virus drug, and proves that the multi-target inhibitor Gidalizie can effectively inhibit replication of the monkeypox virus at a low-toxicity concentration through in-vitro experiments, reveals a new use of Gidalizie as an anti-monkeypox virus drug, and provides an important basis and a candidate compound for development of a new, safe and effective monkeypox treatment drug.

The present application provides compositions of induced pluripotent stem cells (iPSCs) or pancreatic beta cells and poxviruses, as well as methods of making the compositions and methods of using the compositions to treat diseases.

The invention belongs to the technical field of biological medicines, discloses an application of erythromycin ethyl succinate in preparation of a medicine for preventing and / or treating poxvirus infection, and also provides a medicine and a medicine composition containing erythromycin ethyl succinate. The traditional Chinese medicine composition can effectively inhibit interaction between viruses and host cells and improve virus infection symptoms, and has the advantages of filling the blank in the prior art and providing a novel, safe and effective anti-poxvirus treatment scheme.

The present invention is in the field of viral immunotherapy. The invention provides new pseudocowpox (PCPV) viruses, in particular recombinant PCPV, composition thereof as well as their therapeutic use for preventing or treating diseases, and, notably, proliferative diseases like cancers and restenosis and infectious diseases such as chronic ones. The present invention also provides methods for generating and amplifying such a PCPV and a method for eliciting or stimulating and / or re-orienting an immune response using such a PCPV. More specifically, the invention provides an alternative to the existing poxvirus vectors such as MVA (Modified Virus Ankara) and may be largely used for the therapeutic vaccination.

Disclosed in the present invention are a dimethylphosphoryl substituted compound, and a preparation method therefor, a pharmaceutical composition thereof and the use thereof. Provided in the present invention is a compound of formula (I) or a pharmaceutically acceptable salt thereof. The compound of the present invention can target a host eIF2α kinase, eIF2α phosphorylation and protein synthesis. The compound of the present invention has great biological activity for treating breast cancer. Particularly, compound SIPI-27 and compound SIPI-28 of the present invention has inhibitory activity against breast cancer significantly superior to that of the control compounds BTdCPU and neratinib; and / or the compound of the present invention also has biological activity against coronaviruses and / or orthopoxviruses, in particular, compound SIPI-25 of the present invention has broad-spectrum anti-coronavirus activity against porcine epidemic diarrhea virus (PEDV), mouse hepatitis virus (MHV), infectious bronchitis virus (IBV) and porcine deltacoronavirus (PDCoV), and also has activity against the Taterapox virus (TTV) orthopoxvirus.

The invention discloses a primer probe combination for detecting monkey pox virus and branches thereof and application of the primer probe combination, and belongs to the technical field of virus detection. A group of specific primers and probes capable of detecting the monkey pox virus and the branches thereof are successfully designed according to a monkey pox virus genome, and a method for detecting the monkey pox virus and the branches thereof based on multiple real-time fluorescent PCR is established on the basis of the primers and the probes. The method can accurately detect the pathogen of the monkey pox virus clinical sample, and the detection result is completely consistent with the typing result determined by genome sequencing. The detection method provided by the invention is low in cost, effectively reduces manpower and time cost, improves detection efficiency, and has good application prospects in laboratory diagnosis, field detection, health evaluation and the like of viruses.

The invention discloses a monkey pox virus B6-A29 and A35-M1 fusion antigen and application thereof, and belongs to the technical field of biological medicine. The B6-A29 and A35-M1 fusion protein with good stability and uniform quality is designed, the neutralizing antibody activity is remarkably enhanced, the in-vivo protection effect is good, and the long-term protection effect is achieved. Compared with simple superposition of a single protein mixing effect, the method has better humoral immunity and cellular immunity, and the production, purification and quality control processes are simpler, more stable and lower in cost compared with a scheme of respectively producing four independent proteins and then mixing, and more accord with the requirements of vaccine industrial production.

To provide cancer vaccines based on a replication-defective vaccinia virus such as an MVA expressing antitumor neopeptide fusions, and to provide methods for preparing the same.SOLUTION: The present invention relates to a personalized cancer vaccine comprising a recombinant poxvirus encoding one or more neopeptides, or to a composition comprising such a recombinant poxvirus and a pharmaceutically acceptable vehicle, and to use of the personalized cancer vaccine to treat a cancer subject in need thereof. A particular embodiment is a method for providing the vaccine or composition, comprising the steps of: a) extracting DNA from tumor and non-tumor samples; b) selecting a target region, preferably the entire coding region of the genome (exome); c) sequencing the target region (e.g., the exome) from the extracted DNA; and d) identifying one or more tumor-specific mutations by comparing the DNA sequences obtained from the tumor and non-tumor samples.SELECTED DRAWING: None

The present application relates to a multi-immunogen chimeric or mixed antigen for a poxvirus, particularly monkeypox virus, related products, and preparation method and use thereof. The chimeric or mixed antigen of the present application comprises three immunogens: (1) a monkeypox virus A35R protein or an antigenic fragment thereof (or a peptide fragment derived therefrom), (2) a monkeypox virus M1R protein or an antigenic fragment thereof (or a peptide fragment derived therefrom), and (3) a monkeypox virus B6R protein or an antigenic fragment thereof (or a peptide fragment derived therefrom), and can elicit an immune response against two types of infectious virus particles, namely intracellular mature virus particles (IMV) and extracellular envelope virus particles (EEV), thereby efficiently inducing specific immunoprotective effects against the monkeypox virus. Moreover, the poxvirus vaccine of the present application features good safety, rapid response, and scalable production capacity, thus showing excellent clinical application prospects.

This invention provides the application of compound SH in the preparation of broad-spectrum anti-orthopox virus drugs, belonging to the field of biomedical technology. This invention selects monkeypox virus (MPXV-B.1-China-C-tan-CQ01), vaccinia virus WR strain (WR), recombinant vaccinia virus Tiantan strain (TTV) expressing green fluorescent protein, and mousepox virus (ECTV) as representative strains. Through studies on the inhibitory activity of viral nucleic acid replication and infectious viral particles, it was found that compound SH has broad-spectrum anti-orthopox virus activity, laying the foundation for the development of broad-spectrum anti-orthopox virus drugs and possessing significant development value and broad application prospects.

The invention provides an anti-orthopoxvirus neutralizing monoclonal antibody B36B9 and application thereof, the monoclonal antibody is obtained by screening through a flow cytometry sorting technology and a single cell PCR technology, has a unique CDR partition, and is mainly used for recognizing L1R (M1R) antigen protein of orthopoxvirus. The affinity of the antibody to VARV (Vector Activated Receptor Virus), VACV (Vector Activated Receptor Virus), CPXV (Cytopoxvirus) and MPXV (Metapoxvirus) of orthopoxvirus is 0.21 nM, 0.39 nM, 0.03 nM and 0.12 nM respectively. In a virus neutralization experiment, the IC50 of the antibody and mature virions in vaccinia virus cells is 41.13 nM. In a monkey pox virus infected mouse model, the antibody can significantly reduce mouse lung virus titer. The monoclonal antibody provided by the invention has the characteristics of high expression, high affinity and broad spectrum, and has application prospects in preparation of medicines for treating and preventing the monkey pox virus or kits for detecting the monkey pox virus.

The invention relates to the technical field of therapeutic application of nucleoside (acid) analogues, in particular to application of nucleoside (acid) analogues to treatment and / or prevention of orthopoxvirus related diseases. It is proved for the first time that various nucleoside (acid) analogues can be used as vaccinia virus inhibitors; especially for the ancitabine hydrochloride, the antiviral effect of the ancitabine hydrochloride and the combined use of the ancitabine hydrochloride and the tecovirimat is verified through in-vivo and in-vitro experiments. The ancitabine hydrochloride has a relatively high selectivity index on vaccinia virus, and the survival rate of diseased mice is remarkably improved. Through new use of old medicines, the medicine research and development period is greatly shortened; the traditional Chinese medicine composition can be quickly put into use to make up for the deficiency of anti-orthopoxvirus medicines; meanwhile, epidemic of orthopoxvirus can be effectively dealt with, a new treatment scheme is provided for infection of orthopoxvirus (such as VACV), and an important scientific basis is provided for application and research of ancitabine hydrochloride and drugs for combined use of ancitabine hydrochloride and tecovirimat and further inhibition of orthopoxvirus.