66 results about "Pox viruses" patented technology

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 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 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.

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 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 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.

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.

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.

The present invention relates to a mammalian non-human cell line, specifically Chinese hamster ovary (CHO) cells, that is genetically modified to express poxvirus host range genes CP77, K1L and / or SPI-1 which are not expressed in MVA, and to the use of said cell line in the reproduction of MVA.

The present application relates to monkeypox virus human monoclonal antibody and its application, through screening human antibody humanization mouse anti E8L specific binding memory B cell, the human source high neutralization activity monkeypox virus antibody E8L-7H4, E8L-7H2, E8L-7E7, E8L-8D6 and E8L-7C9 obtained, with the characteristics of strong monkeypox virus binding capacity, good in vitro neutralization, affinity, with in vivo protection, completely different from the reported monkeypox virus antibody sequence, provide the product for the detection and neutralization of monkeypox virus, provide the possibility for the monkeypox virus product with in vivo protection.

Provided herein are antibodies and antigen-binding fragments thereof that bind to monkeypox virus (MPXV) protein A35 and / or to vaccinia virus (VACV) protein A33, nucleic acids and vectors encoding such antibodies and antigen-binding fragments, and methods of use. Provided are, for example, methods of reducing or blocking infection of a cell with MPXV or VACV. Also provided are methods of treating or preventing infection with MPXV or VACV.

Provided are a polynucleotide encoding a chimeric or mixed antigen of poxvirus multiple immunogens, a related nucleic acid product thereof, and the use thereof in the preparation of a vaccine for preventing and / or treating poxvirus (in particular monkeypox virus) infection. The chimeric or mixed antigen of the poxvirus multiple immunogens encoded by the polynucleotide comprises two immunogens: a monkeypox virus A35R protein or an antigenic fragment thereof (or an appropriate variant thereof) and a monkeypox virus M1R protein or an antigenic fragment thereof (or an appropriate variant thereof). The immunogen components of the chimeric or mixed nucleic acid vaccine based on the polynucleotide are clear, and the chimeric or mixed nucleic acid vaccine can efficiently stimulate specific immune responses (for example, generating a protective antibody) against poxvirus (in particular monkeypox virus), can be used for preventing and / or treating poxvirus (in particular monkeypox virus), and has high clinical application prospects.

The application provides an RNA, an RNA combination and application thereof, and a multivalent monkeypox vaccine, and relates to the technical field of biotechnology.The mRNA provided by the application is obtained after codon optimization, and can express antigen proteins in vitro cells with high efficiency; the mRNA combination provided by the application has high expression, and after immunizing mice, high-titer neutralizing antibodies against the live virus of the vaccinia virus Tianlu strain can be detected, and the mRNA combination has good immunogenicity, and is of great significance for the prevention of the monkeypox virus.The multivalent monkeypox mRNA vaccine provided by the application can realize stable and safe expression in vivo and effectively activate an immune response, and can cause a neutralizing antibody response, and in the serum of the immunized mice, high-titer neutralizing antibodies against the live virus of the vaccinia virus Tianlu strain can be detected.

An immunoassay is described that enables a precise evaluation of immune responses in individuals exposed to Mpox or vaccinated with MVA, with high sensitivity and specificity. The serological assay targets three Orthopoxvirus antigens, MPXV-B6R, MPXV-A27L, and VACV-B5R, which are sufficient to quantify antibody responses to both MVA-vaccination (VACV-B5R) and, separately, infection (MPXV-B6R). The three antigen titres can be combined in a simple function [sum of ((MPXV-B6R) / VACV-B5R) and (MPXV-A27L)] to provide a numerical test score that can be compared with a reference (threshold) value to differentiate between post infection and post vaccination immune responses.

Provided herein are recombinant modified vaccinia Ankara (rMVA) viral vectors comprising heterologous nucleic acid inserts encoding one or more SARS-CoV2 proteins, peptides, or fragments thereof, operably linked to a promoter compatible with poxvirus expression systems that, upon expression, are capable of inducing protective immunity. The compositions can be used in a priming vaccination strategy or in a prime / boost vaccination strategy to provide immunity to SARS-CoV2 and variants thereof.

The application discloses application of WYE-125132 in preparation of an anti-monkeypox virus drug and belongs to the technical field of biological medicines. The application first finds that WYE-125132 can significantly inhibit replication of monkeypox virus, and the inhibition is dose-dependent. Meanwhile, the WYE-125132 has good anti-monkeypox virus activity, provides important scientific basis and scheme for development of a new, safe and effective monkeypox treatment drug and clinical treatment, and therefore, the WYE-125132 has good application prospect in development of the anti-monkeypox virus drug.

The application provides a glass micropore channel electrochemical aptamer for detecting monkeypox virus and a preparation method and application thereof, and belongs to the technical field of monkeypox virus (MPXV) detection. The glass micropore channel electrochemical aptamer provided by the application comprises a tapered glass micropore channel, the tip of the tapered glass micropore channel is modified with a three-dimensional network of silicon dioxide nanowires, the surface of the silicon dioxide nanowires is modified with an amino group, and a monkeypox virus aptamer with a nucleotide sequence as shown in SEQ ID NO. 1 is fixed on the surface, and the end of the monkeypox virus aptamer is modified with a carboxyl group. The glass micropore channel electrochemical aptamer provided by the application has a detection lower limit of 9x10 ‑15 g / mL for the actual detection of MPXV A29L protein, and has high specificity, stability, repeatability and reproducibility, has the potential to be converted to a rapid diagnosis scene, and provides an efficient and scalable platform for the detection of monkeypox virus protein.

This invention relates to the field of biomedicine, and in particular to the application of disulfiram in the preparation of orthopoxvirus inhibitors. Disulfiram exhibits a significant inhibitory effect on orthopoxvirus by specifically binding to palmitic acid on the MPXV gp045 membrane protein. When the IC50 of disulfiram is 825 nM, it can significantly inhibit the spread of orthopoxvirus. In HeLa and Huh7.5.1 cells, its IC50 is 3022 nM and 7125 nM, respectively, which can significantly inhibit the formation of EEV, thereby preventing the further spread of orthopoxvirus and providing a more comprehensive intervention for anti-orthopoxvirus therapy.

This invention discloses an engineered probiotic outer membrane vesicle vaccine co-expressing multiple antigens of monkeypox virus, its preparation method, and its application. The outer membrane vesicle vaccine is based on... lpxm Using the gene-deleted probiotic Escherichia coli Nissle 1917 as the host, ABM@OMV was constructed by genetically engineering and co-expressing and displaying three key monkeypox virus antigens, A9R, B6R, and M1R, on the surface of its secreted outer membrane vesicles. Leveraging the natural adjuvant and highly efficient mucosal delivery characteristics of OMV, combined with a multi-antigen synergistic strategy, nasal immunization can simultaneously activate strong systemic humoral immunity (high-titer neutralizing IgG) and cellular immunity (CD4+). + / CD8 + T cells are involved in the vaccine, which induces high levels of specific sIgA antibodies in the respiratory and distal genital tract mucosa, forming an effective immune barrier. Challenge experiments showed that the vaccine completely protects mice from lethal doses of vaccinia virus, significantly reduces tissue damage, and provides a novel solution for preventing monkeypox virus transmission via mucosa.