48 results about "Enterovirus" patented technology

The invention discloses a primer group and a kit for simultaneously detecting nucleic acids of various respiratory pathogens based on twenty-six PCR (Polymerase Chain Reaction). The kit comprises primer pool freeze-dried powder of influenza A virus (FluA), influenza B virus (FluB), respiratory syncytial virus (RSV), human parainfluenza virus (hPIV), mycoplasma pneumoniae (MP), novel coronavirus (SARS-CoV-2), human respiratory adenovirus (HADV), human respiratory nose / enterovirus (HRV / HEV), bordetella pertussis (BP), human coronavirus (HCoV), human bocavirus (HBoV) and chlamydia pneumoniae (CP), PCR (polymerase chain reaction) freeze-dried powder and a buffer solution. According to the kit, primer system optimization is carried out on various pathogens, brand new primers and probe pools are designed, clinical sensitivity and specificity can be achieved, and meanwhile, the kit is matched with a fully-closed full-automatic detection card box integrating sample treatment and amplification and is suitable for rapid detection of respiratory tract pathogens.

The invention relates to the technical field of anti-enterovirus medicines, in particular to application of Enractevir in preparation of an anti-enterovirus medicine. According to the invention, efficient screening of candidate drugs is realized through a multi-channel virus reporting system based on a TAT trans-activation effect, and a small molecule compound drug Enractevir with a specific antiviral effect on enterovirus group A 71 and enterovirus group D 68 is obtained. Enractevir improves the interferon secretion level of host cells by inhibiting the activity of enterovirus 2A / 3C protease, thereby inhibiting virus replication and proliferation. Enractevir plays a role through double-target 2A / 3C protease, and the risk of virus drug resistance can be reduced. According to the technical scheme, the technical problem that in the prior art, specific drugs for the two kinds of enteroviruses are lacked can be solved, a standardized treatment scheme is provided for prevention and control of enterovirus related diseases in the global range, and the medicine has remarkable public health significance and wide application and popularization value.

One of the core sequences of a polypeptide inhibitor provided by the present invention is as shown in SEQ ID NO.1, and the sequence of a polypeptide comprising a cell-penetrating peptide is as shown in SEQ ID NO.2. The polypeptide provided by the present invention uses enterovirus 2C protein multimerization as a target. Compared with other inhibitors targeting an enterovirus 2C protein, the present invention has high inhibition efficiency, good safety, and provides a new policy for enterovirus prevention and control.

The invention relates to the technical field of biology, in particular to a primer probe combination product for respiratory tract infection detection. A plurality of specific primers and self-quenching probes are integrated in a single reaction system; simultaneous, rapid and rapid detection on 15 respiratory pathogens (including influenza A virus, influenza B virus, respiratory syncytial virus, severe acute respiratory syndrome coronavirus 2, mycoplasma pneumoniae, parainfluenza virus, rhinovirus, enterovirus, coronavirus, adenovirus, metapneumovirus, bordetella pertussis, bocavirus, chlamydia pneumoniae and chlamydia psittaci) is realized. The detection is accurate.

The invention provides an EVB-IRES-based annular RNA for coding a GLP-1 similar polypeptide and application of the annular RNA, and belongs to the technical field of molecular biology. The invention provides a circGLP1 recombinant plasmid and / or a circGLP1-FcBO recombinant plasmid based on EVB-IRES (Enterovirus Virus B-IRES). The circGLP1 recombinant plasmid comprises nucleotide sequences of Td-3, EVB-3, GLP1, 6xPolyAC, EVB-5 and Td-5, and the circGLP1 recombinant plasmid and the circGLP1-FcBO recombinant plasmid comprise nucleotide sequences of the Td-3, the EVB-3, the GLP1, the 6xPolyAC, the EVB-5 and the Td-5. The circGLP1-FcBO recombinant plasmid contains nucleotide sequences of Td-3, EVB-3, GLP1-FcBO, FcBO-6xPolyAC, EVB-5 and Td-5, and is characterized in that the nucleotide sequences of the circGLP1-FcBO recombinant plasmid are shown in the description. After the circular RNA-LNP is injected, the blood sugar of the mouse is continuously lower than the initial blood sugar within one week, which proves that the circular RNA-LNP can maintain the efficacy in vivo for at least one week.

An in vitro approach for detecting Enterovirus-D68 (EV-D68) is disclosed. In one aspect, two or more EV-D68 genomic regions are amplified with primers that each include a 5' universal tail and an EV-D68-specific sequence (SEQ ID NOs: 47-92). The tails enable indexing and sequencing of tiled amplicons to confirm EV-D68 presence and permit lineage or subclade assignment. In another aspect, a type-specific RT-qPCR assay employs a forward primer (SEQ ID NO: 95), a reverse primer (SEQ ID NO: 96), and a fluorescent probe (SEQ ID NO:97) for rapid detection. Primer sets and kits comprising the primers, probe, and optional reagents are provided for environmental, clinical, or research testing performed outside the body, including wastewater-based surveillance. The universal tails are selected to avoid sequence overlap with any target amplicon. The methods, uses, and kits support sensitive EV-D68 detection across circulating variants and facilitate scalable sequencing and public-health monitoring.

The present invention relates to a self-amplifying RNA construct by which the expression of a target protein is optimized. Compared with traditional mRNA and self-amplification RNA based on the enterovirus, the optimized self-amplification RNA based on the enterovirus has the advantage that the expression level of the target protein is improved. In addition, the multi-antigen self-amplification RNA can simultaneously express one or more target proteins, and the expression rate of the multi-antigen self-amplification RNA is far higher than that of traditional mRNA. Therefore, the self-amplifying RNA constructs according to the present invention can be widely used in vaccines and the like.

The present disclosure describes a sulfate salt form of vapendavir and a pharmaceutical composition containing the same. Methods of treating a subject having a respiratory enterovirus by administering to the subject a pharmaceutical composition including a therapeutically effective amount of the vapendavir sulfate are also described, wherein the subject may or may not also have COPD or asthma.

The invention provides a monoclonal antibody 3G1 capable of specifically recognizing CV-A5 virus and having neutralizing activity and application of the monoclonal antibody 3G1. The monoclonal antibody is prepared from a CV-A5 virus antigen immunized mouse and splenocytes of the mouse through a cell fusion technology, and amino acid sequences of three CDR regions of a heavy chain variable region of the monoclonal antibody sequentially comprise sequences as shown in SEQ ID NO.1-3; the amino acid sequences of the three CDR regions of the light chain variable region sequentially comprise sequences as shown in SEQ ID NO.4-6. The monoclonal antibody can be specifically combined with a CV-A5 virus, and is not combined with enteroviruses such as EV-A71, CV-A10, CV-A6, CV-A16 and the like. The monoclonal antibody targets conformational epitopes, has neutralizing activity, can specifically recognize CV-A5 viruses, is an ideal CV-A5 antigen detection antibody, and is beneficial to acceleration of the research and development process of hand-foot-mouth multivalent vaccines containing CV-A5 pathogens.

The invention provides a universal baculovirus transfer vector and application thereof. The universal baculovirus transfer vector comprises the following elements: (a) a 3CD protease coding gene containing Q184L mutation; (b) a baculovirus homologous repeat region enhancer hr1; (c) a baculovirus late expression factor lev5 gene and an expression regulatory element thereof; (d) a polh-pSel promoter used for driving the expression of the P1 protein; (e) a target serotype enterovirus P1 protein; wherein the elements (a)-(d) constitute a general core skeleton, and the element (e) allows insertion or replacement of a specific P1 protein gene. The 3CD stability is remarkably enhanced, the VLP yield and the assembling efficiency are greatly improved, the method has outstanding universality, and an efficient technical platform is provided for development of broad-spectrum enterovirus vaccines.

The application belongs to the field of pharmaceutical chemical industry and relates to a cyclic peptide compound shown as formula M or a stereoisomer, a tautomer or a mixture thereof of the compound, a pharmaceutically acceptable salt, a polymorph, a co-crystal or a solvate of the compound, or a stable isotope derivative, a metabolite or a prodrug of the compound. The application also relates to a method for synthesizing the cyclic peptide compound and an intermediate. The provided cyclic peptide compound has a strong inhibitory effect on a coronavirus 3CL protease and a small RNA virus (for example, an enterovirus EV71 virus) 3C protease. After cell level activity testing, the provided cyclic peptide compound has an obvious inhibitory effect on EV71 virus and coronavirus and the like, indicating that the cyclic peptide compound shown as formula M can produce a viral inhibitory effect at the cell level by inhibiting viral protease activity, and has a good application prospect as an antiviral drug.

The application discloses application of sulforaphane in preparation of an antienterovirus drug and belongs to the technical field of medicines, wherein the sulforaphane can inhibit the expression of viral proteins, inhibit viral genome replication and inhibit the production of virus particles to achieve the purpose of resisting enteroviruses; specifically, the sulforaphane can inhibit the replication of enteroviruses by up-regulating the content of p53 proteins. In addition, the sulforaphane can also be used for reducing the cell morphological damage caused by enteroviruses.

Disclosed are a compound and an application thereof in the preparation of a medicine for treating enterovirus-related diseases. The compound is the compound represented below by formula I, and can significantly inhibit the 3C protease activity of various enteroviruses. At present, no specific medicine aimed at human enteroviruses has been approved to come to market, and the use of the solution of the present invention can compensate for the insufficiencies of the prior art.

This invention discloses a traditional Chinese medicine composition for assisting in the improvement of hand-foot-mouth disease in infants and young children, belonging to the field of traditional Chinese medicine technology. The composition consists of eight medicinal herbs: lotus leaf, coix seed, angelica dahurica, kudzu root, platycodon root, agastache rugosa, cimicifuga rhizome, and dandelion, with a defined optimal medicinal ratio. Based on the seasonal differences in the pathogenesis of hand-foot-mouth disease, this invention targets the core pathologies of winter (cold congestion of microvessels, water and sodium retention, and internal heat generation) and spring and summer (hypothalamic sympathetic activation, increased heart rate, and visceral heat overload). It also addresses the technical deficiencies of clinical Western medicine, cold-natured traditional Chinese medicine, calamine lotion, and diuretics, such as vasoconstriction, kidney damage, central nervous system disorders, increased skin exudation, and rebound water retention. This invention employs a combination of warming and cooling herbs, regulating the ascending and descending functions, and promoting diuresis and protecting the body's vital energy. The synergistic effects of these herbs can dilate spasmodic microvessels, improve renal perfusion, stabilize abnormal heart rates, stabilize the hypothalamic center, and assist in antagonizing enteroviruses. By targeting and reducing abnormal permeability of skin capillaries with Angelica dahurica and Platycodon grandiflorus, it reduces blood extravasation and inhibits the formation and exudation of herpes from the root cause. This invention has mild medicinal properties, is suitable for all seasons, and has high safety. It can effectively improve symptoms of hand-foot-mouth disease such as fever, herpes, irritability, and cold extremities, reduce the risk of severe illness, antagonize the toxic side effects of commonly used clinical drugs, and is suitable for the delicate constitution of infants and young children, possessing good prospects for clinical application and promotion.

The present invention relates to a bifunctional peptide comprising a virus-binding portion (2) and a mucin-binding portion (1) covalently linked to the virus-binding portion (2). The virus-binding portion is selected from peptides that bind to SARS-CoV-2, influenza A virus, influenza B virus, rhinovirus and other enteroviruses, human parainfluenza virus, and / or metapneuvirus. The mucin-binding portion is selected from lectins such as trefoil factor 3.

The present disclosure describes a sulfate salt form of vapendavir and a pharmaceutical composition containing the same. Methods of treating a subject having a respiratory enterovirus by administering to the subject a pharmaceutical composition including a therapeutically effective amount of the vapendavir sulfate are also described, wherein the subject may or may not also have COPD or asthma.

The present invention discloses a nucleic acid detection kit for simultaneously detecting 9 respiratory pathogens based on a common qPCR detection platform, comprising the following non-mixing: reaction solution A, reaction solution B, and reaction solution C. Reaction solution A includes forward and reverse primers and fluorescent probes for influenza A virus, influenza B virus, and respiratory syncytial virus; reaction solution B includes forward and reverse primers and fluorescent probes for human parainfluenza virus, Mycoplasma pneumoniae, and the new coronavirus; reaction solution C includes forward and reverse primers and fluorescent probes for human respiratory adenovirus, human respiratory rhinovirus / enterovirus, and Bordetella pertussis. The fluorescent groups of the fluorescent probes used for different pathogens in the same reaction solution are different. The nucleic acid detection kit for simultaneously detecting 9 respiratory pathogens based on a common qPCR detection platform of the present invention has high specificity and high sensitivity, and is suitable for rapid detection of respiratory pathogens.

The invention discloses a premature ovarian failure rat animal model building method based on enterovirus group transplantation, and particularly relates to the technical field of animal model building. According to the invention, the enterovirus group of a premature ovarian failure patient is subjected to in-vitro extraction and purification, and then is transplanted into a female rat, so that a new experimental model is provided for researching the interaction between the enterovirus group and the premature ovarian failure; meanwhile, a new way is opened up for further revealing the research on the complex relation between intestinal microorganisms and female reproductive health. In addition, the model is expected to provide an experimental basis for developing a novel treatment strategy for premature ovarian failure. The method aims to deeply explore the relationship between the enterovirus / bacteriophage group and female reproductive system diseases, especially premature ovarian failure.

The application discloses a virus marker for depression diagnosis and a screening method and application thereof, relates to the technical field of biological detection, and the virus marker for depression diagnosis comprises at least one of s_Stenotrophomonas_virus_Pokken, g_Pokkenvirus, s_Dickeya_virus_AD1 and g_Alexandravirus. The application firstly takes the enterovirus group characteristics as the biomarker of depression, breaks through the limitation that traditional mental illness diagnosis relies on subjective scale evaluation; compared with the prior art, the four virus markers can be used for the diagnosis of clinical depression alone or in combination, have the characteristics of non-invasiveness and high sensitivity, can effectively distinguish the depression patients from the healthy people, can early discover the high-risk groups, and provide a new objective diagnosis method for the precise typing of depression.

The invention discloses a recombinant duck enteritis virus for expressing 3-type duck hepatitis A virus immunogenic genes and a construction method and application thereof. The recombinant duck enteritis virus is characterized in that an eukaryotic expression cassette containing a type 3 duck hepatitis A virus immunogenic gene is inserted into a non-coding region between UL26 and USL27 genes of a duck enteritis virus genome. According to the invention, a duck hepatitis A virus (DHAV) immunogenic gene is inserted into a duck enteritis virus (DEV) genome at a fixed point by virtue of a CRISPR / Cas9 gene editing technology, so that the recombinant duck enteritis virus for expressing the duck hepatitis A virus type 3 immunogenic gene is constructed and obtained. Moreover, based on the recombinant duck enteritis virus for expressing the 3-type duck hepatitis A virus immunogenicity gene constructed by the invention, the exogenous DHAV immunogenicity gene can be stably expressed in the recombinant virus, and the recombinant virus has good in-vitro replication ability and hereditary stability and can be used for preparing animal vaccines.

The invention provides a monoclonal antibody capable of specifically recognizing a CV-A5 virus and having neutralizing activity and application of the monoclonal antibody. The monoclonal antibody is prepared from a CV-A5 virus antigen immunized mouse and splenocytes of the mouse through a cell fusion technology, and amino acid sequences of three CDR regions of a heavy chain variable region of the monoclonal antibody are sequentially shown as SEQ ID NO.1-3; the amino acid sequences of the three CDR regions of the light chain variable region are sequentially as shown in SEQ ID NO.4-6. The monoclonal antibody can be specifically combined with a CV-A5 virus, and is not combined with enteroviruses such as EV-A71, CV-A10, CV-A6, CV-A16 and the like. The monoclonal antibody targets conformational epitopes, has neutralizing activity, can specifically recognize CV-A5 viruses, is an ideal CV-A5 antigen detection antibody, and is beneficial to acceleration of the research and development process of hand-foot-mouth multivalent vaccines containing CV-A5 pathogens.

A bifunctional peptide is provided, the bifunctional peptide comprising a virus binding moiety and a mucin binding moiety covalently bound to the virus binding moiety. The virus binding moiety is chosen from peptides binding to SARS-CoV-2, to influenza A, to influenza B, to rhinoviruses and other enteroviruses, to human parainfluenza virus, and / or to metapneuvirus. The mucin binding moiety is chosen from lectins such as trefoil factor 3.

The application provides a broad-spectrum monoclonal antibody of enterovirus A population and application thereof, and belongs to the technical field of molecular biology and immune analysis. The monoclonal antibody comprises the following six CDR regions: the amino acid sequences of the CDR regions of the heavy chain are respectively shown in SEQ ID No. 1-SEQ ID No. 3; and the amino acid sequences of the CDR regions of the light chain are respectively shown in SEQ ID No. 4-SEQ ID No. 6. The application also provides a nucleotide fragment encoding the monoclonal antibody, a recombinant vector and an engineering cell line comprising the nucleotide fragment, an antibody conjugate and their uses. The monoclonal antibody is a non-neutralizing antibody of IgG1 subtype, can be combined with enterovirus A population viruses in a broad spectrum, and can be used for preparing a reagent or / and a kit for detecting enterovirus A population viruses, and for preparing a medicine for inhibiting, preventing or / and treating enterovirus A population viruses.

The invention discloses a group of immunogenic peptides with an anti-tumor immune response activating function as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The amino acid sequences of the immunogenic peptide are SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 and SEQ ID NO: 4, and the immunogenic peptide is obtained by the following steps: extracting an enterovirus-like particle (VLPs) preparation from excrement of a healthy mouse, giving the preparation to a tumor model mouse through intragastric administration, and separating and screening from ileum tissues of the mouse by using a liquid chromatography-mass spectrometry technology. The VLPs can be migrated to tumor tissues and presented as the immunogenic peptide through tumor cell MHC-I molecules, so that CD8 + T cells are efficiently activated, a tumor immune microenvironment is remodeled, and tumor growth is inhibited. Experiments show that the immunogenic peptide shows a remarkable anti-tumor effect when being used alone or combined with a PD-1 inhibitor, and the tumor inhibition rate of drug combination can reach 89.4% and is remarkably superior to that of single treatment.

A kind of compound containing N-(substituted sulfonyl) acetamide structure as shown in formula I, its pharmaceutically acceptable salt, its isomer, its hydrate or its solvate, and its application as viral protease inhibitor in preparation of antiviral drugs.The provided peptide compound has strong inhibitory effect on coronavirus 3CL protease and small RNA virus (such as enterovirus EV71 virus) 3C protease.Through cell level activity test, the N-(substituted sulfonyl) acetamide structure compound has obvious inhibitory effect on small RNA virus (such as enterovirus EV71 virus) virus and coronavirus, etc., as shown in formula I, the compound containing N-(substituted sulfonyl) acetamide structure can produce viral inhibition effect on cell level by inhibiting viral protease activity, and has good antiviral drug application prospect.

The present disclosure provides a set of primers and optional probes for identifying the presence of alpha-coronavirus, beta-coronavirus, SARS-CoV-2, adenovirus, chlamydia pneumoniae, influenza A, influenza B, metapneumovirus, rhinovirus / enterovirus, mycoplasma, Bordetella, parainfluenza, and respiratory syncytial virus (RSV), the present invention relates to nucleic acid probes, which may be included with a cartridge (e.g., in a kit) or in a cartridge, for automated detection of these pathogens by nucleic acid amplification. The disclosure also provides related detection methods, as well as kits, systems, and kits useful in such methods.

The invention discloses an application of dihydromyricetin or a derivative thereof in preparation of a broad-spectrum enterovirus pathogen resisting medicine. The dihydromyricetin or the derivative thereof serving as the allosteric inhibitor of the 3C protease can non-competitively inhibit the enzyme activity of 3C proteins of various viruses of enteroviruses in a broad-spectrum manner, so that the replication of related viruses is influenced, and the dihydromyricetin or the derivative thereof has remarkable broad-spectrum inhibition activity on various viruses in the enteroviruses and has very high safety; the compound can be developed as a novel safe and effective antiviral drug and lead compound, and has a wide application prospect.

To provide a VLP vaccine derived from the genus Enterovirus which is safe and has good stability.SOLUTION: The VLP vaccine of the present invention is highly safe because it uses VLPs having no viral internal gene as an antigen, and has good stability because it is fixed with formaldehyde in a high salt concentration.SELECTED DRAWING: None

The application discloses a method for GI and GII type norovirus on-site typing detection, comprising the following steps: in the presence of primers, carrying out double RT-RPA reaction on a template, then adding the amplification product after reaction into a CRISPR / Cas12a detection system of GI and GII type norovirus respectively, carrying out fluorescence analysis, and completing GI and GII type norovirus on-site typing detection. The application covers each subtype of norovirus GI and GII, has no cross reaction with common gastroenteritis viruses such as rotavirus and enterovirus, can effectively distinguish the two genotypes of GI and GII, and has no off-target phenomenon, and the minimum detection limit of the application for the GI and GII genotype norovirus is 10 2 copies / µL and 1 copies / µL respectively. The whole detection process can be completed within 35 min under the condition of 37 DEG C constant temperature, can be directly used for on-site detection by means of an ultraviolet flashlight, and does not need laboratory instruments and professional operation.

The invention discloses an application of an atestin diterpenoid compound Agallochaol Q. The atestin diterpenoid compound Agallochaol Q has remarkable inhibitory activity on enteroviruses (especially EV-D68), so that the atestin diterpenoid compound has a relatively great development prospect and a relatively great research value in the aspect of resisting the EV-D68, and the atestin diterpenoid compound Agallochaol Q has a relatively good application prospect in resisting the enteroviruses (especially the EV-D68). The compound is expected to be further designed and developed into a novel anti-EV-D68 medicine in the future.