Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving virus or bacteriophage
Patent
1998-04-20
2000-10-31
Park, Hankyel
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving virus or bacteriophage
435335, 4353391, 4241481, 4241601, 4242081, 53038835, 53038822, 5303894, C12Q 170, C12N 506, A61K 3940, A61K 3942, C07K 1600
Patent
active
061400432
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to pharmaceutical compositions for competitively inhibiting the binding of a retrovirus, preferably HIV, to the IFN-receptor of a target cell. Preferably, said pharmaceutical compositions comprise a protein, polypeptide or equivalent molecule or a combination thereof which binds to the IFN-.alpha./.beta.-receptor or to HIV-gp41. Furthermore, the present invention relates to the use of said protein, polypeptide or equivalent molecule or IFN-.beta. or a combination thereof for the preparation of a pharmaceutical composition for preventing or treating retroviral infections. The present invention also relates to a combination of substances for the diagnosis of a HIV infection which is based on the detection of the interaction between HIV-gp41 and the IFN-.alpha./.beta.-receptor.
Since the discovery of the human immunodeficiency virus (HIV) as the etiological agent of AIDS, there have been many advancements in the understanding of the replicative cycle of HIV and in the design of antiviral drugs. The development and application of such antiviral pharmaceutical compositions that inhibit the replication of HIV are based on the knowledge of the replicative cycle of HIV: The first step in HIV replication is access of the retrovirus to the organism through exposure to HIV-infected blood or body fluids. The envelope glycoprotein gp120 which plays a major role, selectively binds to it's receptor CD4, a cell-surface protein located on a subpopulation of helper T lymphocytes. After binding, the HIV virus enters the susceptible cells. The virus is uncoated within the cytoplasm of these cells yielding viral genomic RNA which is transcribed by virus-encoded reverse transcriptase into single-stranded DNA. Then, this single-stranded DNA is duplicated, and, after degradation of the RNA strand by ribonuclease H, proviral (unintegrated) circular double stranded DNA is formed. The proviral DNA can then migrate into the nucleus of the host cell and become integrated into the genome. After a latency period RNA polymerases of the host cell transcribe the DNA of the integrated HIV into mRNA, which is then translated into viral proteins. After translation the precursor proteins are further modified (specific cleavage by virus-specific proteins and glycosylation by host enzymes) and the viral proteins are assembled in the cytoplasm. After budding of the virus from the host cell surface additional cells are infected and the cycle is repeated.
Known targets in the replicative cycle of HIV for therapeutic intervention include binding of the target cell and entry (previous agents: soluble CD4, SCD4-PE40), reverse transcription of the retrovirus (inhibitors: Zidovudine, Nevirapine etc.), transcription and translation (inhibitors: Trichosanthin, tat-antagonists, anti-sense oligonucleotides etc.) and viral maturation and budding (inhibitors: N-butyl-DNJ, protease inhibitors).
Furthermore, interferons (IFN) are used for therapeutic intervention of HIV infection, since they interact on different levels of the HIV replication cycle (reviewed in Pitha, Antiviral Res. 24 (1994), 205-219).
However, although progress has been made in developing drugs and therapies for treating, retroviral, for example, HIV infections, effective pharmaceutical compositions without severe side effects are still lacking.
Thus, the technical problem underlying the present invention is to provide new compounds for the prevention, treatment and diagnosis of retroviral, preferably HIV, infections which overcome the disadvantages of the prior art compounds.
The solution to said technical problem is achieved by providing the embodiments characterised in the claims. It has been, surprisingly, found that a retrovirus does not only interact with the CD4 receptor of target cells but that there exists a different type of interaction, namely between the IFN-receptor of the target cell and retroviral envelope protein(s) which seems to be independent of the CD4-interaction. Thus, HIV should be able to enter and infect every cell type, since IFN recepto
Chen Ying-Hua
Dierich Manfred P.
Park Hankyel
Rentschler Biotechnologie GmbH
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