50 results about "Viral life cycle" patented technology

In one aspect, the invention provides methods and compositions for the expression of small RNA molecules within a cell using a retroviral vector. The methods can be used to express double stranded RNA complexes. Small interfering RNA (siRNA) can be expressed using the methods of the invention within a cell, that interfere with a viral life cycle by down regulating either the viral genome, a viral genome transcript, or a host cell that. In another aspect the invention provides methods for treating patients having suffering from infection, particularly infection with HIV.

In one aspect, the invention provides methods and compositions for the expression of small RNA molecules within a cell using a retroviral vector. The methods can be used to express double stranded RNA complexes. Small interfering RNA (siRNA) can be expressed using the methods of the invention within a cell, that interfere with a viral life cycle by down regulating either the viral genome, a viral genome transcript, or a host cell that. In another aspect the invention provides methods for treating patients having suffering from infection, particularly infection with HIV. In a further aspect, the invention provides methods for producing siRNA encoding lentivirus where the siRNA activity may interfere with the lentiviral life cycle.

Fusion of the viral envelope, or infected cell membranes with uninfected cell membranes, is an essential step in the viral life cycle. Recent studies involving the human immunodeficiency virus type 1(HIV-1) demonstrated that synthetic peptides (designated DP-107 and DP-178) derived from potential helical regions of the transmembrane (TM) protein, gp41, were potent inhibitors of viral fusion and infection. A computerized antiviral searching technology (C.A.S.T.) that detects related structural motifs (e.g., ALLMOTI 5, 107x178x4, and PLZIP) in other viral proteins was employed to identify similar regions in the Epstein-Barr virus (EBV). Several conserved heptad repeat domains that are predicted to form coiled-coil structures with antiviral activity were identified in the EBV genome. Synthetic peptides of 16 to 39 amino acids derived from these regions were prepared and their antiviral activities assessed in a suitable in vitro screening assay. These peptides proved to be potent inhibitors of EBV fusion. Based upon their structural and functional equivalence to the known HIV-1 inhibitors DP-107 and DP-178, these peptides should provide a novel approach to the development of targeted therapies for the treatment of EBV infections.

The present invention provides for the treatment or prevention of Hepadnaviridae infection and disease caused by Hepadnaviridae infection. In particular, the invention provides compositions and methods that affect the ability of Hepadnaviridae to utilize the host's cellular machinery as part of the virus' lifecycle. The invention relates to the discovery that interfering with the normal ability of viruses to utilize the host cell machinery with LSD1 inhibitors reduces HBV replication. Thus, the treatment and prevention of Hepadnaviridae infection and disease caused by Hepadnaviridae according to the invention comprises administering to an individual in need of treatment, a therapeutically effective amount of a LSD1 inhibitor. The individual in need of treatment can be a human or, e.g., another mammal.

Methods and compositions for treatment, diagnosis, and prevention of a virus comprise administering to a patient antibodies which react with regions of viral proteins and result in neutralization of infectivity and inactivation of functionally essential events in the life cycle of the virus. The antibodies recognize viral epitopes which fail to elicit an immune response in man when encountered through infection or naturally through the environment. In a preferred embodiment, the invention provides compositions and methods useful in the treatment and diagnosis of human immunodeficiency virus (HIV) infections.

Fusion of the viral envelope, or infected cell membranes with uninfected cell membranes, is an essential step in the viral life cycle. Recent studies involving the human immunodeficiency virus type 1 (HIV-1) demonstrated that synthetic peptides (designated DP-107 and DP-178) derived from potential helical regions of the transmembrane (TM) protein, gp41, were potent inhibitors of viral fusion and infection. A computerized antiviral searching technology (C.A.S.T.) that detects related structural motifs (e.g., ALLMOTI5, 107x178x4, and PLZIP) in other viral proteins was employed to identify similar regions in the respiratory syncytial virus (RSV). Several conserved heptad repeat domains that are predicted to form coiled-coil structures with antiviral activity were identified in the RSV genome. Synthetic peptides of 16 to 39 amino acids derived from these regions were prepared and their antiviral activities assessed in a suitable in vitro screening assay. These peptides proved to be potent inhibitors of RSV fusion. Based upon their structural and functional equivalence to the known HIV-1 inhibitors DP-107 and DP-178, these peptides should provide a novel approach to the development of targeted therapies for the treatment of RSV infections.

The invention includes compositions and methods useful for treatment of a virus infection in a mammal by double-targeting the virus (i.e. targeting the virus at more than one stage of the virus life cycle) and thereby inhibiting virus replication. The compositions of the invention include compounds which comprise a phosphocholine moiety covalently conjugated with one or more antiviral agents (e.g. nucleoside analogue, protease inhibitor, etc.) to a lipid backbone. The invention also includes pharmaceutical compositions and kits for use in treatment of a virus infection in mammals. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the invention, in an amount effective to treat the infection, to a mammal infected with a virus. Additionally, the invention includes compositions and methods useful for combating a cancer in a mammal and for facilitating delivery of a therapeutic agent to a mammalian cell. The compositions of the invention include compounds which comprise an alkyl lipid or phospholipid moiety covalently conjugated with an anticancer agent (e.g. a nucleoside analogue). The invention also includes pharmaceutical compositions and kits for combating a cancer and for facilitating delivery of a therapeutic agent to a mammalian cell. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the invention, in an amount effective to combat a cancer or to facilitate delivery of a therapeutic agent to a mammalian cell.

The invention includes compositions and methods useful for treatment of a virus infection in a mammal by double-targeting the virus (i.e. targeting the virus at more than one stage of the virus life cycle) and thereby inhibiting virus replication. The compositions of the invention include compounds, which comprise a phosphocholine moiety covalently conjugated with one or more therapeutic agents (e.g. nucleoside analogue, protease inhibitor, etc.) to a lipid backbone. The invention also includes pharmaceutical compositions for use in treatment of a virus infection in mammals. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt or a prodrug thereof, or a pharmaceutical composition of the invention, in an amount effective to treat the infection, to a mammal infected with a virus. Additionally, the invention includes compositions and methods useful for combating a cancer in a mammal and facilitating delivery of a therapeutic agent to a mammalian cell. The compositions of the invention include compounds, which comprise an alkyl lipid or phospholipid moiety covalently conjugated with a therapeutic agent (e.g., a nucleoside analogue). The invention also includes pharmaceutical compositions for combating cancer and facilitating delivery of a therapeutic agent to a mammalian cell. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt or a prodrug thereof, or a pharmaceutical composition of the invention, in an amount effective to combat a cancer or to facilitate delivery of a therapeutic agent to a mammalian cell.

The invention includes compositions and methods useful for treatment of a virus infection in a mammal by double-targeting the virus (i.e. targeting the virus at more than one stage of the virus life cycle) and thereby inhibiting virus replication. The compositions of the invention include compounds which comprise a phosphocholine moiety covalently conjugated with one or more antiviral agents (e.g. nucleoside analogue, protease inhibitor, etc.) to a lipid backbone. The invention also includes pharmaceutical compositions and kits for use in treatment of a virus infection in mammals. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the invention, in an amount effective to treat the infection, to a mammal infected with a virus. Additionally, the invention includes compositions and methods useful for combating a cancer in a mammal and for facilitating delivery of a therapeutic agent to a mammalian cell. The compositions of the invention include compounds which comprise an alkyl lipid or phospholipid moiety covalently conjugated with an anticancer agent (e.g. a nucleoside analogue). The invention also includes pharmaceutical compositions and kits for combating a cancer and for facilitating delivery of a therapeutic agent to a mammalian cell. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the invention, in an amount effective to combat a cancer or to facilitate delivery of a therapeutic agent to a mammalian cell.

In one aspect, the invention provides methods and compositions for the expression of small RNA molecules within a cell using a retroviral vector (FIG. 1A). The methods can be used to express double stranded RNA complexes. Small interfering RNA (siRNA) can be expressed using the methods of the invention within a cell, that interfere with a viral life cycle by down regulating either the viral genome, a viral genome transcript, or a host cell that. In another aspect the invention provides methods for treating patients having suffering from infection, particularly infection with HIV. In a further aspect, the invention provides methods for producing siRNA encoding lentivirus where the siRNA activity may interfere with the lentiviral life cycle.

Compositions that bind viral proteins that are specifically expressed during the latent stage of the viral life cycle are disclosed. These compositions bind the latent viral proteins while the viral proteins are expressed in their cellular host, and provide a means for targeting cells that harbor latent virus. In a preferred embodiment the compositions are antibodies which bind the extracellular region of the latent viral protein, most preferably LMP-2A, an EBV latent protein, which are conjugated to a diagnostic or cytotoxic agent or immobilized to a solid support for removal of the infected cells. These antibodies are capable of distinguishing cells expressing EBV DNA from cells which are not expressing EBV DNA. Compositions that can be used to elicit production of these antibodies, or as a vaccine, are also disclosed. Methods for generating diagnostic or cytotoxic reagents and vaccines based on the viral epitopes that identify cells harboring latent virus are also disclosed. The antibody conjugates can be used in diagnostic assays to identify cells expressing latent viral protein and people who are harboring latent viral particles. The antibody conjugates can also be used to remove the infected cells or to kill the infected the cells. Alternatively, or in addition, the viral proteins or portions thereof can be used as a vaccine to induce an immune reaction by the host to kill the infected cells. These methods can be used to detect or treat patients harboring latent viruses like EBV and who are at risk of developing a disease such as an autoimmune disease like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

The present invention features a cell-based assay that recapitulates all aspects of a viral lifecycle for use in identifying antiviral agents. The assay employs synchronized, non-dividing host cells and a fluorescence resonance energy transfer peptide substrate for monitoring endogenous viral protease activity, which is indicative of viral infection kinetics.

The invention provides siRNA for targeted regulation and control of HBV gene expression and application of the siRNA. The double-stranded RNAi agent comprises an antisense strand and a sense strand complementary to the antisense strand forming a double-stranded region, and the nucleotide sequence of the antisense strand is as shown in SEQ ID NO: 8, or the nucleotide sequence of the antisense strand is a modified sequence of the sequence as shown in SEQ ID NO: 8. Cell and animal experiment results show that the double-stranded RNAi agent provided by the invention can significantly reduce the expression of one or more HBV genes and block the life cycle of viruses, and can be used for developing drugs for treating HBV gene expression related diseases.

Nucleic acid constructs comprising viral genomic nucleic acid which comprises at least two endogenous gene expression regulatory units which each comprise an endogenous promoter where the endogenous promoters of the units are active at the same phase in the viral life cycle of the virus the viral genomic nucleic acid is derived from are provided. The endogenous gene expression regulatory units are used to express particular chosen heterologous coding sequences and in particular to express heterologous antigens. The constructs can be used in a vaccine to generate an immune response against the heterologous antigens and in particular may be used in a DNA vaccine. Methods for generating the constructs and means for their administration are also provided.

Zika virus (Zika virus, ZIKV) belongs to flaviviridae flaviviruses, and in recent years, Asian lineage viruses of Zika virus are spread to a plurality of countries in the world from South America andthe like. ZIKV infection is associated with Green-Barie syndrome and some birth defects, including forehead syndrome and the like. A reverse genetic system is an important tool for researching virus life cycle, pathogenesis, vaccine research and development and antiviral drugs, but toxicity and instability of cDNA clone of flavivirus genome in transformed bacteria are always a technical difficultyfor hindering construction of infectious clone. According to the invention, a genetically stable eukaryotic-started ZIKV full-length infectious clone ZG01 is constructed. The ZG01 reverse genetic system provides a platform and a research tool for researching a ZIKV life cycle, ZIKV-host interaction, vaccine and antiviral drug research and development. The construction method can also provide scientific reference for construction and research of reverse genetics systems of other flaviviruses or RNA viruses.

One approach to treating individuals infected with HIV-1 is to administer to such individuals compounds that directly interfere with and intervene in the machinery by which HIV-1 replicates itself within human cells. Although the specific role of HIV-1 viral protein Vif in the viral life cycle is not known, the vif gene is essential for the pathogenic replication of lentiviruses in vivo. The present invention relates to a method for treating an individual exposed to or infected with HIV-1. Individuals identified as being exposed to or infected by HIV-1 are administered a therapeutically effective amount of one or more compounds that inhibit or prevent replication of said HIV-1 by interfering with the replicative or other essential functions of HIV-1 viral protein Vif by interactively blocking the multimerization domain of Vif, thereby preventing multimerization of Vif protein, which is important for Vif function in the lentivirus life cycle. In preferred embodiments, the compound or compounds that interactively block the multimerization domain of Vif are Vif antagonists. Pharmaceutical compositions comprising these compounds are also disclosed.

Nucleic acid constructs comprising viral genomic nucleic acid which comprises at least two endogenous gene expression regulatory units which each comprise an endogenous promoter where the endogenous promoters of the units are active at the same phase in the viral life cycle of the virus the viral genomic nucleic acid is derived from are provided. The endogenous gene expression regulatory units are used to express particular chosen heterologous coding sequences and in particular to express heterologous antigens. The constructs can be used in a vaccine to generate an immune response against the heterologous antigens and in particular may be used in a DNA vaccine. Methods for generating the constructs and means for their administration are also provided.

Compositions that bind viral proteins that are specifically expressed during the latent stage of the viral life cycle are disclosed. These compositions bind the latent viral proteins while the viral proteins are expressed in their cellular host, and provide a means for targeting cells that harbor latent virus. In a preferred embodiment the compositions are antibodies which bind the extracellular region of the latent viral protein, most preferably LMP-2A, an EBV latent protein, which are conjugated to a diagnostic or cytotoxic agent or immobilized to a solid support for removal of the infected cells. These antibodies are capable of distinguishing cells expressing EBV DNA from cells which are not expressing EBV DNA. Compositions that can be used to elicit production of these antibodies, or as a vaccine, are also disclosed. Methods for generating diagnostic or cytotoxic reagents and vaccines based on the viral epitopes that identify cells harboring latent virus are also disclosed. The antibody conjugates can be used in diagnostic assays to identify cells expressing latent viral protein and people who are harboring latent viral particles. The antibody conjugates can also be used to remove the infected cells or to kill the infected the cells. Alternatively, or in addition, the viral proteins or portions thereof can be used as a vaccine to induce an immune reaction by the host to kill the infected cells. These methods can be used to detect or treat patients harboring latent viruses like EBV and who are at risk of developing a disease such as an autoimmune disease like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

A method of modulating viral RNA replication and translation, in a eukaryotic cell, of positive-strand viral RNA, comprising the step of contacting a viral RNA-binding protein (vRbp) with a compound that modulates an activity of said protein.

Provided is a virus infection model with which the shortcomings of conventional hepatitis virus infection models are overcome. The present invention provides a method for building a virus infection model with which it is possible to reproduce a viral life cycle, including infecting, with the virus, a cell aggregate formed by culturing tissue or organ cells in vitro. The virus infection model is avirus infection model with which it is possible to reproduce a viral life cycle including a cell aggregate infected with the virus, wherein the cell aggregate is formed by culturing tissue or organ cells in vitro. The present invention provides a method for screening for substances possessing antiviral activity by using the virus infection model.

Fusion of the membrane of enveloped viruses with the plasma membrane of a receptive host cell is a prerequisite for viral entry and infection and an essential step in the life cycle of all enveloped viruses, such as paramyxoviruses. The instant invention is directed to providing polypeptides which are a heptad portion of a Henipavirus F protein effective against fusion between a membrane of a paramyxovirus and a plasma membrane of a cell. The instant invention also provides nucleic acids, compositions, and methods effective against paramyxovirus infection. Accordingly, the instant invention provides therapeutic agents and vaccines effective against paramyxoviruses viruses, especially HeV or NiV.

The invention discloses a multi-target intervention-based plant compound gynecological anti-HPV (human papillomavirus) gel preparation, which comprises two parts, namely a compound plant extracting solution and an aqueous gel carrier, the compound extracting solution is derived from rheum officinale, scutellaria baicalensis, coptis chinensis, golden cypress, radix sophorae flavescentis, fructus cnidii, alum, gallnut, common carpesium fruit, radix angelicae, cortex dictamni, fructus kochiae, frankincense and myrrh; the anti-HPV gel preparation is obtained by mixing and stirring according to the proportion. Aiming at an intervention window that a patient is continuously infected but does not deteriorate to an operation stage, intervention is carried out by adopting an action mechanism of local epithelial micro-ecological restoration and mucosal immunity, E6 / E7 oncogenic protein expression is inhibited, L1 capsid assembly is damaged, key nodes of a virus life cycle are covered, and escape risks are reduced by multi-target collaborative anti-HPV (Human Papilloma Virus); by inhibiting an NF-kB / EMT signal axis, the cervical lesion progress risk is reduced; the safety is high and the curative effect is obvious.

The invention relates to the technical field of biological medicine, in particular to application of GW4064 in preparation of drugs for resisting porcine reproductive and respiratory syndrome virus. The invention discloses a novel application of a farnesyl ester X receptor stimulant GW4064 in preparation of a PRRSV (porcine reproductive and respiratory syndrome virus) resisting medicine. The GW4064 has strong antiviral activity on PRRSV (Porcine Reproductive and Respiratory Syndrome Virus), and particularly has a remarkable inhibition effect on a high-pathogenicity strain (HP-PRRSV). The GW4064 interferes with the life cycle of the virus by targeting the NSP3 protein of the PRRSV, so that the replication and propagation of the virus are inhibited. The GW4064 has a remarkable antiviral effect on various variants of the PRRSV, and shows a broad-spectrum antiviral effect. Meanwhile, the GW4064 is small in molecular weight, can easily enter cells, and can efficiently play a role without carrier delivery. The invention also provides a pharmaceutical composition taking GW4064 as a main active component, and a theoretical basis and a practical basis are provided for development of PRRSV antiviral drugs.

The invention provides application of a pharmaceutical composition in preparation of anti-influenza virus drugs, and belongs to the technical field of biological medicines. The invention provides a pharmaceutical composition of carabrone, panax japonicus saponin IVa and plantamajoside. Multi-target intervention is realized aiming at key stages (such as adsorption, replication and release) of an influenza virus life cycle. Experiments show that the composition can significantly inhibit replication and proliferation of influenza viruses. The natural component composition disclosed by the invention has the advantage of higher safety, provides a safer, effective and economic treatment choice for clinic, and has remarkable conversion value and market potential.

An antisense oligonucleotide and the use thereof. A series of ASOs are designed on the basis of the genome sequence of a hepatitis B virus (HBV), and are modified by means of using a specific modification mode. Cell and animal experiment results show that some modified ASOs obtained by means of using the specific modification mode can significantly reduce the expression of one or more HBV genes and block the life cycle of viruses, and therefore can be used to develop drugs for treating HBV infection-related diseases.

This disclosure provides siRNAs that target and regulate HBV gene expression and their applications. The double-stranded RNAi agent comprises an antisense strand and a sense strand complementary to the antisense strand forming the double-stranded region. The nucleotide sequence of the antisense strand is shown in SEQ ID NO:13, or the nucleotide sequence of the antisense strand is a modified sequence of the sequence shown in SEQ ID NO:13. Cellular and animal experimental results show that the double-stranded RNAi agent provided in this disclosure can significantly reduce the expression of one or more HBV genes, block the viral life cycle, and can be used to develop drugs for treating HBV gene expression-related diseases.

The present disclosure provides siRNA targeting the regulation of HBV gene expression and applications thereof. The double-stranded RNAi agent comprises an antisense strand and a sense strand complementary to the antisense strand to form a double-stranded region, wherein the nucleotide sequence of the antisense strand is set forth in SEQ ID NO: 8, or the nucleotide sequence of the antisense strand is a modified sequence of the sequence set forth in SEQ ID NO: 8. The results of cell and animal experiments show that the double-stranded RNAi agent provided by the present disclosure can significantly reduce the expression of one or more HBV genes, block the viral life cycle, and be used for the development of drugs for treating diseases related to HBV gene expression.

The invention provides siRNA for targeted regulation and control of HBV gene expression and application of the siRNA. The double-stranded RNAi agent comprises an antisense strand and a sense strand complementary to the antisense strand forming a double-stranded region, and the nucleotide sequence of the antisense strand is as shown in SEQ ID NO: 13, or the nucleotide sequence of the antisense strand is a modified sequence of the sequence as shown in SEQ ID NO: 13. Cell and animal experiment results show that the double-stranded RNAi agent provided by the invention can significantly reduce the expression of one or more HBV genes and block the life cycle of viruses, and can be used for developing drugs for treating HBV gene expression related diseases.