65 results about "Human coronavirus" patented technology

The present invention belongs to the field of biomedicine, and relates to polypeptides capable of inhibiting human coronavirus infections, particularly to polypeptides capable of inhibiting human coronavirus infections in a broad spectrum manner, and applications thereof. According to the present invention, the polypeptides capable of providing broad spectrum inhibition effects for infections caused by more than 2 human coronaviruses are provided based on the conservation property of the S2 region of a coronavirus S protein and the similar fusion mechanism; the test results show that the polypeptides can achieve the commonality of the human coronavirus, ie., the similar HR region and the same fusion mechanism mediated by the coronavirus S protein so as to provide a series of HCoV-EK polypeptides, wherein the polypeptides provide good inhibition effects for currently popular human coronaviruses, and further provide good inhibition activity for SARS virus (RsSHC014-CoV or RsW1V1-CoV) possibly infecting human; and the polypeptides of the present invention can provide the prevention and treatment candidate drug for the currently popular human coronaviruses and the novel human coronavirus possibly emerging in the future.

Antiviral protease inhibitors, including peptidyl aldehydes, peptidyl α-ketoamides, peptidyl bisulfite salts, and peptidyl heterocycles, are disclosed, along with related antiviral compounds, and methods of using the same to treat or prevent viral infection and disease. The compounds possess broad-spectrum activity against viruses that belong to the picornavirus-like supercluster, which include important human and animal pathogens including noroviruses, enteroviruses, poliovirus, foot-and-mouth disease virus, hepatitis A virus, human rhinovirus (cause of common cold), human coronavirus (another cause of common cold), transmissible gastroenteritis virus, murine hepatitis virus, feline infectious peritonitis virus, and severe acute respiratory syndrome coronavirus.

Antiviral protease inhibitors, including macrocylic transition state inhibitors and peptidomimetics are disclosed, along with related antiviral compounds, and methods of using the same to treat or prevent viral infection and disease. The compounds possess broad-spectrum activity against viruses that belong to the picornavirus-like supercluster, which include important human and animal pathogens including noroviruses, sapoviruses, enteroviruses, poliovirus, foot-and-mouth disease virus, hepatitis A virus, human rhinovirus (cause of common cold), human coronavirus (another cause of common cold), transmissible gastroenteritis virus, murine hepatitis virus, feline infectious peritonitis virus, and severe acute respiratory syndrome coronavirus.

The invention provides a method for single-tube multiplex fluorescent polymerase chain reaction (PCR) detection of human coronavirus OC43, 229E, NL63, HKU1 and SARS. The method adopts primers having sequences of SEQ ID NO: 1-10, and probes having sequences of SEQ ID NO: 11-15. The invention also provides a kit for single-tube multiplex fluorescent PCR detection of human coronavirus OC43, 229E, NL63, HKU1 and SARS. The kit contains the primers and the probes. The method provided by the invention adopts the primers which are specific primers of OC43, 229E, NL63, HKU1 and SARS, and the probes which are Taqman probes, utilizes TAMRA / CY5 / FAM / ROX / JOX multiple fluorescein labeling, realizes single-tube multiplex detection of human coronavirus OC43, 229E, NL63, HKU1 and SARS, and has the advantages of strong specificity, high sensitivity, fast detection speed, simple and convenient operation and low cost. The primers and the probes can be used as detection reagents for a scientific research and clinical application.

Antiviral protease inhibitors, including peptidyl aldehydes, peptidyl α-ketoamides, peptidyl bisulfate salts, and peptidyl heterocycles, are disclosed, along with related antiviral compounds, and methods of using the same to treat or prevent viral infection and disease. The compounds possess broad-spectrum activity against viruses that belong to the picornavirus-like supercluster, which include important human and animal pathogens including noroviruses, enteroviruses, poliovirus, foot-and-mouth disease virus, hepatitis A virus, human rhinovirus (cause of common cold), human coronavirus (another cause of common cold), transmissible gastroenteritis virus, murine hepatitis virus, feline infectious peritonitis virus, and severe acute respiratory syndrome coronavirus.

Disclosed herein is a newly isolated human coronavirus (SARS-CoV), the causative agent of severe acute respiratory syndrome (SARS). Also provided are the nucleic acid sequence of the SARS-CoV genome and the amino acid sequences of the SARS-CoV open reading frames, as well as methods of using these molecules to detect a SARS-CoV and detect infections therewith. Immune stimulatory compositions are also provided, along with methods of their use.

Antiviral protease inhibitors, including macrocylic transition state inhibitors and peptidomimetics are disclosed, along with related antiviral compounds, and methods of using the same to treat or prevent viral infection and disease. The compounds possess broad-spectrum activity against viruses that belong to the picornavirus-like supercluster, which include important human and animal pathogens including noroviruses, sapoviruses, enteroviruses, poliovirus, foot-and-mouth disease virus, hepatitis A virus, human rhinovirus (cause of common cold), human coronavirus (another cause of common cold), transmissible gastroenteritis virus, murine hepatitis virus, feline infectious peritonitis virus, and severe acute respiratory syndrome coronavirus.

The invention relates to probes and assays which are used for the simultaneous detection, in a single assay sample, of a plurality of nucleic acid sequences of viruses that cause respiratory infections in humans, selected from among influenza virus type A, influenza virus type B, influenza virus type C, human respiratory syncytial virus type A, human respiratory syncytial virus type B, human adenovirus, human parainfluenza virus type 1, human parainfluenza virus type 2, human parainfluenza virus type 3, human parainfluenza virus types 4A and 4B, enterovirus, rhinovirus, human coronavirus type 229E, human coronavirus type OC43, coronavirus that causes severe acute respiratory syndrome (SARS), human metapneumovirus and combinations thereof.

The invention relates to a quadruple fluorescence quantitative detection kit for simultaneously detecting four human coronaviruses, and belongs to the technical field of human coronavirus detection. The human coronaviruses specifically include HCoV-229E / HCoV-NL63 / HCoV-OC43 / HCoV-HKUI. The detection kit specifically includes four specific primer pair and probe groups, a positive quality control product and a negative quality control product. Each specific primer pair and probe group comprises a specific primer pair and a probe sequence. The positive quality control product is specifically an artificially synthesized target sequence; the negative quality control product is deionized water or sterile water. According to the kit, the four human coronaviruses can be simultaneously detected by asingle tube, so that the detection specificity is high, the detection sensitivity is high, the detection time is short, and the defects of long consumed time, high detection cost, easy cross contamination and the like caused by one-by-one detection are avoided. At present, no similar related products are reported in the market. The kit has wide application prospects in the aspects of disease detection, infectious disease prevention and control, clinical treatment guidance and the like.

The invention discloses a multiple reverse transcription real-time fluorescence quantitative PCR (RT-qPCR) kit and a special primer probe composition for distinguishing a novel coronavirus (SARS-CoV-2), severe acute respiratory syndrome coronavirus (SARS-CoV) and four kinds of common human coronaviruses (including human coronavirus 229E (HCoV-229E), human coronavirus NL63 (HCoV-NL63), human coronavirus HKU1 (HCoV-HKU1) and human coronavirus OC43 (HCoV-OC43), and a use method of the kit and the composition. According to the kit, a single-tube four-color fluorescence multiple RT-qPCR method is adopted for detecting and distinguishing coronaviruses aiming at a human respiratory tract sample. The coronavirus typing detection kit disclosed by the invention is short in detection period, high insensitivity and good in typing effect; quality monitoring of sample extraction and amplification processes can be realized by monitoring human RNA internal reference B2M genes, and false positive results caused by aerosol pollution are reduced by utilizing a dUTP-UNG enzyme anti-pollution system.

The invention provides primers and probes or a combination thereof of fluorescent quantitative PCR that can be used to detect diseases caused by human coronavirus and respiratory syncytial virus. In aspecific embodiment, the sequences of the primers and probes are as shown in SEQIDNOs: 1-3, and / or as shown in SEQIDNOs: 4-6, and / or as shown in SEQIDNOs: 7-9. The invention also provides applicationof the primers and probes or the combination thereof to preparation of reagents for detecting human coronavirus OC43, human coronavirus HKU1 and / or respiratory syncytial virus RSVB in samples.

The invention relates to a method of developing a main proteinase SARS inhibitor. Human coronaviruses are major causes of upper respiratory tract illnesses in humans, in particular, the common cold. Recent investigations have shown that a novel coronavirus causes the Severe Acute Respiratory Syndrome (SARS), a disease that is characterized by high fever, malaise, rigor, headache, non-productive cough or dyspnea, which is rapidly spreading. Within the scope of the invention, based on the structural analysis of the binding mode of the SARS Mpro enzyme, a group of prototype inhibitors is provided that acts as suitable drugs targeting a majority of viral infections of the respiratory tract, including SARS.

The invention designs a pair of degenerate primers hCoV-For and hCoV-Rev applied to universal qualitative detection of human coronavirus in a genomic polymerase gene coding region (1b region) by virtue of comparison analysis of six human coronavirus complete genomic nucleotide sequences logged in GenBank. An upstream primer sequence hCoV-For is as follows: ATGGGWTGGGAYTAYCCHAARTGTG; and downstream primer sequence hCoV-Rev is as follows: TGYTGKGARCARAAYTCRTGWGG; the size of an amplification target fragment is 605bp; RNA of positive specimens of HCoV-229E, HCoV-OC43, HCoC-NL63 and HCoV-HKU1 are respectively extracted for testing the universal primer by One-step RT-PCR. Results show that four human coronavirus RNAs are used as templates, and hCoV-For and hCoV-Rev are used as the universal primers for carrying out One-step RT-PCR reaction, a single target strip with the size about 606p can be amplified; by carrying out sequencing validation of PCR products, results show that the amplification sequence is right without cross reaction. The universal primer sequence can be applied to quick and qualitative detection of nucleic acid of human coronavirus infection.

The invention relates to the field of biomedicine, in particular to application of MERS-CoV 3CLpro (Middle East respiratory syndrome coronavirus 3C-like protease) as a deubiquitinating enzyme and interferon inhibitor. The invention provides a novel deubiquitinating enzyme and interferon inhibitor; the new understanding of the functionality of human coronavirus proteinase can be expanded; theoretical basis can be provided for the research on coronavirus and host antiviral natural immunization and the research on antiviral drugs using viral proteinase as a target.

The invention provides a detecting kit for influenza viruses A and B, human metapneumovirus and human coronaviruses NL63, HKU1 and OC43. The detecting kit comprises a specific pathogen primer and a pathogen gene probe. The detecting kit for influenza viruses A and B, human metapneumovirus and human coronaviruses NL63, HKU1 and OC43 is used for carrying out RT-PCR (Reverse Transcription-Polymerase Chain Reaction) by using the specifically designed pathogen primer and pathogen gene probe on the basis of a multi-fluorescent real-time PCR and Tem-PCR technology, so that the amplification efficiency can be greatly increased to ensure that the detected result can still have very high detecting sensitivity by using a common TaqDNA polymerase, and furthermore, the problems of low amplification efficiency and low detecting sensitivity of the traditional multi-PCR are solved.

The invention relates to a quadruple fluorescent quantitative detection kit capable of simultaneously detecting four human coronaviruses including 2019-nCoV, and belongs to the technical field of detection. The detection kit is applied to RT-PCR / qRT-PCR detection. The detection kit specifically comprises four specific primer pairs, four probes and a positive quality control product. Each of four human coronaviruses correspond to one pair of specific primers and one probe sequence; and the positive quality control product is specifically an artificially synthesized target sequence. Sterile water or ultrapure water is taken as a negative quality control product. The quadruple fluorescent quantitative detection kit can be used for rapidly and simultaneously screening four human coronaviruses2019-nCoV / MERS-CoV / HCoV-OC43 / HCoV-HKUI and has the advantages of high detection sensitivity, strong specificity, simplicity in operation, convenience in application and the like, and the multiple rapid detection can be realized.

The invention relates generally to the field of virology, and relates to the identification and characterization of the targets involved in the evasion strategy of viruses and to the use thereof in methods to identify anti-viral compounds. More in particular to identify compounds which are modulators of myosin light chain kinase (MLCK), a target within said entry and immune-evasion strategy. Other aspects of the invention are directed to anti-viral compounds identified using the models and methods of the present invention, as well as to the use thereof in treating viral infections, such as for example caused by the feline infectious peritonitis virus (FIPV), a coronavirus which belongs to an antigenic group which comprises in particular feline enteric coronavirus (FECV), canine coronavirus (CCV), swine transmissible gastroenteritis coronavirus (TGEV), porcine respiratory coronavirus (PRCV) and human coronavirus (HCV), and which induces, in a host-dependent manner, a range of symptoms which range from mild enteritis to the severe debilitating disease, and, in some cases, up to death. In a particular aspect the present invention provides the use of MLCK inhibitors for the treatment of feline infectious peritonitis (FIP).

Disclosed herein is a newly isolated human coronavirus (SARS-CoV), the causative agent of severe acute respiratory syndrome (SARS). Also provided are the nucleic acid sequence of the SARS-CoV genome and the amino acid sequences of the SARS-CoV open reading frames, as well as methods of using these molecules to detect a SARS-CoV and detect infections therewith. Immune stimulatory compositions are also provided, along with methods of their use.

The present invention relates to the field of medicinal biological engineering technology, and is a DNA vaccine pVPH for preventing SARS virus. It is composed of human coronavirus HE protein antigenic determinant code sequence and signal peptide code sequence of plasminogen activator TPA to form secreted HE protein antigenic determinant code sequence HE-P, then inserting it into the eukaryotic expression vector. Said recombinant plasmid transformed competence colibacillus DH5 alpha is the pVPH engineering bacterium which can be used for preparing vaccine pVPH. Because its expressed antigenic protein can be secreted to the exterior of cell, so that it raises the immunity of body fluid, and can have the better action for preventing infection of SARS virus.

The present invention provides a composition and method for use in the prevention or treatment of a coronaviral infection and in particular, the human coronavirus infection termed severe acute respiratory syndrome (SARS) coronavirus (SARS-HCoV). A method of treating a coronaviral infection is provided through the administration of interferon, further the use of interferons in the treatment of a coronaviral infection is also provided. Preferred forms of interferon for use in the invention are multi-subtype interferon products such as multi-subtype, human alpha-interferon derived from white blood cells commercially available as Multiferon.

The invention provides a human antibody specifically binding to a human coronavirus spike protein receptor binding domain (RBD). Coronavirus RBD-specific memory B cells are isolated from peripheral blood mononuclear cells (PBMCs) of a 5-bit novel coronavirus infected rehabilitation person, amplification is performed to obtain a light and heavy chain variable region sequence of 49 antibodies, and transient expression analysis is performed on 34 of the 49 antibodies, wherein 15 of the antibodies are capable of specifically binding to the coronavirus RBD, and at least 3 of the antibodies are capable of blocking the binding of the coronavirus RBD to the receptor ACE2.

The invention belongs to the field of drug treatment, and particularly relates to application of ethyl p-hydroxybenzoate in preparation of drugs for preventing or treating virus infectious diseases. The invention discloses application of ethyl p-hydroxybenzoate and an inhalation preparation thereof in treatment of coronavirus infectious diseases. The new application of the ethyl p-hydroxybenzoate inhalation solution is verified in a mouse test infected with human coronavirus HCoV-229E, the technical scheme has novelty, a curative effect test of the m-cresol inhalation solution in treatment of pneumonia caused by HCoV-229E virus infection is carried out, and the result shows that the m-cresol inhalation solution can be used for treating pneumonia caused by HCoV-229E virus infection. The ethyl p-hydroxybenzoate inhalation solution shows a good drug effect on the lung index and the inhibition rate of a pneumonia mouse infected with the HCoV-229E virus, and the lung index of the mouse can be remarkably reduced.

The invention discloses application of a pharmaceutical composition containing chlorogenic acid in preparation of antiviral drugs. Experiments prove that the pharmaceutical composition containing the chlorogenic acid can resist viruses. The pharmaceutical composition containing the chlorogenic acid is high in oral bioavailability, and oral drug kinetic parameters of the raw material chlorogenic acid are improved. The pharmaceutical composition containing the chlorogenic acid can obviously inhibit weight loss of virus infected mice, reduce lung indexes, inhibit lung tissue inflammatory factors, resist inflammatory storm, reduce the virus load of lung tissues and resist damage of influenza A viruses and human coronavirus to lungs.

The invention provides a polypeptide containing an amino acid sequence shown in SEQ ID NO: 1. The invention also provides a derivative of the polypeptide modified by palmitic acid or cholesterol. The polypeptide can inhibit infection of a novel 2019 coronavirus (SARS-CoV-2) and various human coronaviruses, and can also inhibit infection of a type I human immunodeficiency virus (HIV-1). The polypeptide provided by the invention has broad-spectrum antiviral activity and has higher stability than PEG modified polypeptide, and the invention aims to provide good prevention and treatment medicine reserve for SARS-CoV-2 which is still popular at present and a mutant strain of the SARS-CoV-2 as well as SARS-related viruses and human immunodeficiency viruses which are likely to break out in the future.

The invention discloses a prediction method of a mutation site of virus adaptive to a human host, and application thereof, and in particular relates to adaptive mutation of virus adaptive to a human host, and application thereof as a drug target and a biomarker. The fact that animal host coronavirus exists in a target attacked by human lung tissue miRNA is found for the first time in the invention; human coronavirus loses targets on these genome through the adaptive mutation so as to get the capability of spreading in the human host; the site of the coronavirus adaptive mutation provided by the invention can be used as a drug design target for treating or preventing coronavirus infection, and a biomarker for checking the coronavirus host range; simultaneously, the algorithm for predictingthe target attacked by the host miRNA on the virus genome provided by the invention can be used for predicting RNAi sensitive targets of all kinds of virus; and the drug design target for treating andpreventing corresponding virus infection and the host range checking biomarker are developed.

The invention discloses a respiratory virus detection kit. The detection kit is used for detecting ORF1ab area and N region of SARS-COV-2 viruses; the detection kit includes the following primers andprobes: amplification primers ORF1ab-F, ORF1ab-R and ORF1ab-probe used for amplifying the ORF1ab area; and amplification primers N-F, N-R and N-probe used for amplifying the N region. Through the adoption of areal-time fluorescence quantitative PCR technology, the detection kit can be used for rapidly detection whether a to-be-detected sample is a new coronavirus positive sample. Detection resultsare accurate by using the detection kit; and therefore, the detection kit has important reference significance of rapid diagnosis on the infection status of SARS-COV-2 human coronavirus.

The invention belongs to the technical field of medicines, and particularly relates to application of exocarpium citri rubrum expectoration extract in preparation of a medicine for inhibiting human coronavirus infection. The invention provides application of exocarpium citri rubrum expectoration extract in preparation of the medicine for inhibiting human coronavirus infection, and experiments show that the exocarpium citri rubrum expectoration extract can inhibit mRNA overexpression of human coronavirus-induced inflammatory factors TNF-alpha, IL-6, IL-8 and IFN-alpha, so that the human coronavirus is inhibited.

A canine respiratory coronavirus (CRCV) that is present in the respiratory tract of dogs with canine infectious respiratory disease and which has a low level of homology to the enteric canine coronavirus, but which has a high level of homology to all bovine coronavirus strains (e.g., Quebec and LY138) and human coronavirus strain OC43.