218 results about "Viral replication" patented technology

This article provides a combination of compounds that can inhibit influenza virus replication, reduce influenza virus load, and / or treat influenza.

The invention belongs to the technical field of medicines, and discloses application of a compound in prevention and treatment of coronavirus infection and / or diseases caused by coronavirus. In particular discloses application of one or more of G96-69, G96-70, G102-35, G110-74, G115-49 and G118-1 in prevention and treatment of coronavirus infection and diseases caused by the coronavirus, improvement of symptoms caused by the coronavirus and in-vitro inhibition of coronavirus replication in a non-treatment destination, and the G96-69, the G96-70, the G102-35, the G110-74, the G115-49 and the G118-1 have relatively good effects in the aspect of resisting the coronavirus. EC50 for inhibiting mouse hepatitis virus MHV is less than 6 [mu] M; the EC 50 of the HCoV-OC43, the EC 50 of the HCoV-229E and the EC 50 of the HCoV-NL63 which are inhibited by the G96-69 and the G96-70 are all smaller than 2 [mu] M.

This invention generally relates to a novel RNA / mRNA production and amplification method using viral RNA replicase and / or RNA-dependent RNA polymerase (RdRp) enzymes as well as the associated mRNAs thereof. The present invention can be used for manufacturing and amplifying all varieties of RNA / mRNA sequences carrying at least an RdRp-binding site in the 5′- or 3′-end, or both. The RNA / mRNA so obtained is useful for not only producing mRNA vaccines and / or RNA-based medicines but also for generating the mRNA-associated proteins, peptides, and / or antibodies under an in-vitro as well as in-cell translation condition. Principally, the present invention is a novel RNA replicase-mediated RNA / mRNA amplification method, namely Replicase Cycling Reaction (RCR). The RNA replicases involved in RCR include but not limited to viral and / or bacteriophage RNA-dependent RNA polymerases (RdRp), particularly coronaviral and hepatitis C viral (HCV) RdRp enzymes.

This invention discloses the application of the DNAL1 gene as a target in screening drugs for the prevention and treatment of Zika virus or dengue virus type 2 infection, specifically the application of screening drugs for the prevention and / or treatment of Zika virus or dengue virus type 2 infection with the aim of inhibiting or knocking out the DNAL1 gene. The invention has found that the DNAL1 gene is a key host factor promoting the replication of Zika virus or dengue virus type 2, and that inhibiting the DNAL1 gene through siRNA or knocking out the DNAL1 gene through CRISPR / Cas9 can inhibit the replication of Zika virus or dengue virus type 2. The DNAL1 gene is a potential host factor for flaviviruses, and this invention provides a potential target for the prevention and / or treatment of Zika virus or dengue virus type 2 infection.

This disclosure relates to a method for preparing intermediates useful for preparing compounds that inhibit the function of human immunodeficiency virus (HIV) during the viral replication cycle, such as by disrupting the function of the HIV capsid shell. [Formula 1] JPEG2026524821000058.jpg39145

The present application provides the use of raltitrexed in the manufacture of a medicament for the treatment of diseases caused by adenovirus infection, including but not limited to respiratory tract infection, gastrointestinal infection and keratitis caused by adenovirus. When raltitrexed was tested for its anti-adenovirus activity at the cellular level, using a viral infection dose of 100 TCID50, the viral infectivity was determined on a human non-small cell lung cancer cell line (A549 cell) model, and the results showed that raltitrexed had a significant inhibitory effect on adenovirus, with an EC 50 = 8.98 nM, a CC 50 > 187.5 nM, and it was found that it had a significant inhibitory effect on the entry of the virus into the cell; and in the hDSG2 mouse model, a significant inhibitory effect of raltitrexed on viral replication was also observed. Therefore, raltitrexed can be used to treat diseases caused by adenovirus infection.

A cassette for the delivery of one or more mRNA is provided, the cassette comprising a 5' UTR, a Nodamura replicon, a ribosomal skipping polynucleotide, the one or more mRNA, a plant virus assembly origin polynucleotide ("OAS"), and a 3' UTR. In one aspect, the cassette further comprises a 5'mRNA cap. In a yet further aspect, the cassette does not comprise a poly A tail.

Described herein is an oncolytic herpes simplex virus, G47ΔhIL12A, which is G47Δ containing a cassette expressing a transgene, e.g., human IL-12, driven by a spontaneously arising genetically altered HCMV immediate-early (IE) enhancer / promoter. This virus has augmented (A) production of the transgene and increased virus replication while retaining safety. Also provided are methods of use thereof for treating cancer, e.g., glioblastoma (GBM) and triple-negative breast cancer (TNBC).

The present application relates to viral sensitizers. More specifically, the present application relates to compounds of Formula (I), as well as methods of using such compounds as viral sensitizers, specifically for increasing permissiveness of a cell to the production of virus from reverse genetics systems, replicating viruses and increasing transduction.

The present invention relates to processes for preparing intermediates useful in the preparation of compounds that inhibit human immunodeficiency virus (HIV) function (e.g., disrupt HIV capsid function) during the viral replication cycle.

The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, thereof:which inhibit coronavirus replication activity. The invention further relates to pharmaceutical compositions comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof, and methods of treating or preventing a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.

Provided herein are RNA molecules encoding viral replication proteins and antigenic proteins or fragments thereof. Also provided herein are compositions that include RNA molecules encoding viral replication proteins and antigenic proteins or fragments thereof, and lipids. RNA molecules and compositions including them are useful for inducing immune responses.

The invention discloses an influenza reporter virus carrying a fluorescent RNA aptamer and a construction method and application thereof, and the influenza reporter virus carrying the fluorescent RNA aptamer is obtained by introducing a termination codon TAA into the 328th nucleotide of an ORF region of an NS1 gene on the basis of a genome of an influenza A virus and terminating in advance, then introducing a terminating codon TAA into the 328th nucleotide of the ORF region of the NS1 gene of the influenza A virus; original nucleotides at the 328-480 sites are replaced by forward or reverse RNA aptamers, and the RNA aptamer is obtained. The influenza reporter virus carrying the fluorescent RNA aptamer constructed by the invention also has the characteristics of good virus replication ability, high RNA imaging sensitivity and good specificity on the basis of stable inheritance, can be used for real-time visual observation of virus RNA, and is used for research on virus replication cycle and molecular mechanism related to the virus RNA. Besides, the construction method of the influenza reporter virus carrying the fluorescent RNA aptamer can also be applied to construction of RNA fluorescent reporter viruses of other subtype influenza viruses such as H3N2 and H5N1, and an important tool is provided for real-time tracing of corresponding virus RNA.

The invention discloses an application of estramustine sodium phosphate (EMP) in preparation of a drug for treating rotavirus, and discovers that the estramustine sodium phosphate (EMP) can significantly inhibit replication of rotavirus and can play an excellent anti-rotavirus effect at a lower IC50; as the biological safety of the EMP is excellent, it is found that the EMP can almost completely inhibit rotavirus replication within the safe concentration, and it is found that the EMP not only significantly inhibits transcription of rotavirus, but also can reduce expression of VP6 protein. Thus, EMP can be used to treat rotavirus.

The invention belongs to the technical field of medicines, and particularly relates to pyrrolo [2, 3-d] pyrimidine compounds of aryl fragments and piperidine fragments as well as a preparation method and application of the pyrrolo [2, 3-d] pyrimidine compounds. The pyrrolo [2, 3-d] pyrimidine compound containing the aryl fragment and the piperidine fragment is an HIV-1 reverse transcriptase inhibitor, and the pyrrolo [2, 3-d] pyrimidine compound further comprises pharmaceutical salt, hydrate and solvate of the pyrrolo [2, 3-d] pyrimidine compound, polycrystal or eutectic of the pyrrolo [2, 3-d] pyrimidine compound, and precursors and derivatives with the same biological functions of the pyrrolo [2, 3-d] pyrimidine compound. The invention also relates to a preparation method of the compound and application of a composition containing one or more of the compounds in related medicines for treating AIDS and the like. The result of an in-vitro cellular level anti-HIV-1 activity experiment shows that the micromolecule has relatively strong anti-HIV-1 biological activity, can remarkably inhibit virus replication in MT-4 cells infected by HIV-1 viruses, and has relatively low cytotoxicity.

The invention belongs to the technical field of virus and gene engineering, and particularly relates to an expression vector of a respiratory syncytial virus (RSV) ON1 genotype consensus sequence strain and an editing strain, a reverse genetic manipulation system and an application of the reverse genetic manipulation system of the respiratory syncytial virus ON1 genotype consensus sequence strain and the editing strain of the RSV ON1 genotype consensus sequence strain and the editing strain of the respiratory syncytial virus ON1 genotype consensus sequence strain. According to the invention, an RSV-ON1 genotype consensus sequence strain is firstly constructed and saved, on the basis, 72 nucleotides which are repeatedly inserted into a G gene of the consensus sequence strain are removed through a gene editing technology, and two strains with different virus G gene sequences are obtained. According to the invention, through construction of RSV infectious clone edited by RSV-ON1 genotype G gene and rescue of the two strains, a fast, simple and accurate RSV reverse genetic system is constructed, and the RSV reverse genetic system can be applied to research on RSV in-vitro virus replication mechanism and pathogenesis and neutralizing antibody immune escape. A etiological technical platform is provided for research, development and evaluation of RSV vaccines, antibodies, drugs and the like.

The present application belongs to the field of genetic engineering and biological medicine technology, and particularly relates to a biomaterial for regulating HTRA1 gene expression and application thereof in antiviral. Specifically, the present application finds that inhibiting HTRA1 gene can significantly promote replication of H13N2 subtype influenza virus, thereby promoting infection of H13N2 subtype influenza virus, while overexpression of HTRA1 can effectively inhibit replication of H13N2 subtype influenza virus, reduce virus titer, and thus improve the ability to resist influenza virus infection, so that the HTRA1 gene can be used as a key target for regulating replication of H13N2 subtype influenza virus, and thus has good practical application value.

The invention discloses a nucleoside antiviral NHC diester prodrug as shown in a formula I and pharmaceutically acceptable salts thereof, and a preparation method and medical application of the nucleoside antiviral NHC diester prodrug. Pharmacological experiments prove that the compound disclosed by the invention has relatively strong inhibitory activity on replication of multiple RNA viruses. Particularly, the compound has good lung microsome release efficiency, the species difference of the lung release efficiency is small, the consistency of the in-vivo drug effect of the antiviral drug and the in-vivo drug effect of the antiviral drug can be improved, and the risk of species difference of prodrug release antiviral active ingredients is avoided. Therefore, the compound provided by the invention has good broad-spectrum antiviral activity, and can be used as a broad-spectrum antiviral drug for treating various respiratory virus infections.

The invention discloses application of a gp130 inhibitor in preparation of a medicine for treating virus infection, and relates to the technical field of medicines. Experiments prove that combination of IL-6 family cell factors and a gp130 receptor is inhibited, so that downward signal transmission of a JAK2 / STAT3 signal channel triggered by the IL-6 family cell factors is inhibited, the purposes of inhibiting cell fusion induced by SARS-CoV-2 spike protein and further influencing replication and propagation of SARS-CoV-2 are achieved, and a small-molecule inhibitor SC144 is an inhibitor of gp130, has a remarkable effect of inhibiting SARS-CoV-2 virus replication and has a good application prospect. Meanwhile, the traditional Chinese medicine composition also has a remarkable effect of inhibiting replication of viruses such as human immunodeficiency virus, herpes simplex virus and respiratory syncytial virus.

To provide high throughput assays for measuring adenovirus replication kinetics.SOLUTION: Recombinant adenovirus genomes containing a heterologous open reading frame (ORF) and a self-cleaving peptide coding sequence are described. The recombinant adenovirus genomes, and recombinant adenoviruses produced by the disclosed genomes can be used, for example, in high- throughput assays to measure virus replication kinetics. Methods for measuring replication kinetics of a recombinant adenovirus are also described. In one aspect, provided are recombinant adenovirus genomes that include a heterologous ORF and a self-cleaving peptide coding sequence, both operably linked to and in the same reading frame as an endogenous adenovirus ORF.SELECTED DRAWING: None

The invention discloses a PDCoV-S1 recombinant protein antigen as well as a preparation method and a vaccine thereof, and belongs to the technical field of recombinant protein vaccines. The amino acid sequence of the PDCoV-S1 recombinant protein antigen disclosed by the invention is as shown in SEQ ID NO: 1; the nucleotide sequence of the PDCoV-S1 recombinant protein antigen is as shown in SEQ ID NO: 2. The vaccine provided by the invention only contains recombinant PDCoV-S1 protein and does not contain genetic materials of viruses, so that all risks of virus replication, virulence reversion or gene recombination are fundamentally avoided. Live viruses do not need to be operated in the production process, so that the biological safety risk and the requirement on the production environment are greatly reduced. The constructed stable CHO engineering cell strain is combined with a serum-free suspension culture technology, so that high-density, large-scale and standardized production of the PDCoV-S1 protein can be realized in a bioreactor. The production process is stable and reliable, the batch-to-batch consistency is good, and the uncertainty and volatility caused by the virus culture link of the traditional vaccine are overcome.

This invention relates to the fields of environmental monitoring and biosafety technology, and in particular to a viral aerosol sampling patch for face masks, comprising: a capture layer for intercepting viral aerosol particles in the air; a culture layer disposed inside the capture layer, the culture layer comprising a culture unit supporting the virus to maintain activity and replicate in the presence of a host, a host bacterium sensitive to the virus, and a visual indicator indicating viral replication or host response; and a base layer disposed inside the culture layer; the sampling patch is fixed to the face mask through the base layer, and viral aerosol collection is achieved without external power through the capture layer, and countable detection results are generated after sampling through the culture layer; utilizing the airflow and humidity conditions naturally formed during wearing, effective interception, activity preservation, and visual detection of viral aerosols are achieved without complex equipment and additional operating steps, and the operation is simple and repeatable.

The application provides a KRT31 gene knockout cell line and its application in promoting replication of viruses of the Picornaviridae family and / or production of vaccines of viruses of the Picornaviridae family, and belongs to the technical field of genetic engineering. The application provides an application of a KRT31 gene or a coded protein thereof as a target in preparation of a product for regulating replication of viruses of the Picornaviridae family and / or vaccine production. Up-regulation of the expression level of the KRT31 gene can inhibit replication of viruses of the Picornaviridae family, and down-regulation of the expression level of the KRT31 gene can promote replication of viruses of the Picornaviridae family. The application adopts sgRNA to knockout the KRT31 gene to prepare a cell line with lost function of a gene coded protein, so as to promote replication of viruses of the Picornaviridae family, improve virus titer and antigen yield, and help to efficiently prepare vaccines of viruses of the Picornaviridae family.

A compound exhibiting coronavirus 3CL protease inhibitory activity or a pharmaceutically acceptable salt thereof, represented by Formula (I)wherein Ring A is a ring represented by:wherein X is a single bond or the like, R2 is substituted or unsubstituted aromatic carbocyclyl or the like, R3c is substituted or unsubstituted aromatic carbocyclyl or the like, R3 is substituted or unsubstituted aromatic carbocyclyl or the like, R3a is a hydrogen atom or the like, R3b is a hydrogen atom, R8a is substituted or unsubstituted aromatic carbocyclyl or the like, and R8b is a hydrogen atom or the like,R1 is a substituted or unsubstituted aromatic heterocyclyl, m is 0 or the like, R5a is each independently a hydrogen atom or the like, R5b is each independently a hydrogen atom or the like, R6 is cyano or the like, and R7a and R7b are each independently a hydrogen atom or the like.

The invention provides application of o8G in blocking EV71 virus replication, and belongs to the technical field of biology. The o8G can well influence the replication of the EV71 virus, can reduce the stability of virus RNA (Ribonucleic Acid), and can provide a new thought for the development of anti-EV71 virus medicines.

The invention relates to the technical field of microorganisms, in particular to a Wehonor coccus ZSJB6 and application thereof. The Villonella sp. ZSJB6 provided by the invention is a new species of the Villonella sp. ZSJB6, a culture supernatant of the Villonella sp. ZSJB6 has a good inhibition effect on VSV virus replication, and results of hemolysis experiments and cytotoxicity experiments show that the strain meets safety requirements, and a new means can be provided for preventing and treating VSV infection.

The present invention provides a compound exhibiting coronavirus 3CL protease inhibitory activity or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the same. Furthermore, the present invention provides a crystalline form useful as an active pharmaceutical ingredient, and a pharmaceutical composition comprising the same.A compound represented by Formula (I):wherein Y is N or the like; R1 is substituted or unsubstituted aromatic heterocyclyl or the like; R2 is substituted or unsubstituted aromatic carbocyclyl or the like; R3 is substituted or unsubstituted aromatic heterocyclyl or the like; —X— is —NH— or the like; m is 1 or the like; R5a is each independently a hydrogen atom or the like; R5b is each independently a hydrogen atom or the like; n is 1 or the like; R4a is each independently a hydrogen atom or the like; and R4b is each independently a hydrogen atom or the like,or a pharmaceutically acceptable salt thereof.

This application relates to the field of biomedical detection technology, specifically to a combination of biomarkers for assessing the severity of viremia in Chikungunya virus patients and its application. The combination of biomarkers for assessing the severity of viremia in Chikungunya virus patients includes one or more of the following biomarkers: TAP1, ISG15, CMPK2, GBP4, OTOF, and SIGLEC1. The biomarker combination provided in this application can objectively and quantitatively reflect the activity of viral replication and the strength of the immune response in the patient, thereby achieving accurate assessment of the severity of viremia. This solves the problem in existing technologies that mainly rely on qualitative or semi-quantitative detection of viral nucleic acids and lack assessment methods closely related to the host's pathological state.

The invention discloses an application of methyl protocatechuate in preparation of a product for treating and / or preventing respiratory syncytial virus infection. The methyl protocatechuate is a natural product, is good in permeability, small in toxic and side effects and simple in structure, can effectively inhibit replication and infection of the respiratory syncytial virus and reduce inflammatory response of a body, can target FTO and inhibit FTO protein expression, and provides a new direction for treating infection of the respiratory syncytial virus.

This invention belongs to the field of genetic engineering, specifically relating to the application of RSAD1 gene / protein as a target in screening drugs to inhibit infection by microribonucleoviridae viruses. This invention unexpectedly discovered that silencing the RSAD1 gene can significantly inhibit Seneca virus replication, and can be used as a target for the development of antiviral drugs against Seneca virus. This invention provides an sgRNA sequence targeting the RSAD1 gene, and combined with CRISPR-Cas9 gene editing technology, silences the RSAD1 gene, obtaining an RSAD1 gene knockout monoclonal cell line. This cell line can significantly inhibit Seneca virus replication, providing a target for further screening of drugs and reagents to resist Seneca virus replication. Simultaneously, this invention found that overexpression of the RSAD1 protein in host cells can significantly promote Seneca virus replication, and can be used as a production cell line for Seneca virus or vaccines.