       Document 0711
 DOCN  M94A0711
 TI    Molecular targets for HIV therapy.
 DT    9412
 AU    Rosenberg M; SmithKline Beecham Pharmaceutical, King of Prussia,
       Pennsylvania; 19406-0939.
 SO    Annu Conf Australas Soc HIV Med. 1993 Oct 28-30;5:25 (abstract no.
       SPI-3). Unique Identifier : AIDSLINE ASHM5/94348944
 AB    There continues to be an urgent need for the discovery and design of
       better drugs with antiviral activities against the HIV viruses. The
       various stages of the HIV life cycle provide specific molecular targets
       for which novel assays and mechanistic approaches can be developed to
       search for and identify new inhibitory agents. For example, viral
       replication, integration, gene expression, and maturation are dependent
       on the presence and function of specific virally encoded gene products
       such as the reverse transcriptase, required for RNA-dependent DNA
       synthesis prior to integration of the pro-viral DNA into the host
       genome; integrase, the enzyme responsible for the integration event; the
       TAT and REV regulatory proteins involved in transactivating viral gene
       expression within the host; and protease, the enzyme responsible for
       proteolytic maturation of the viral precursor polyproteins. In addition,
       viral recognition and entry into human cells also provides certain
       molecular targets for potential intervention. For example, the
       interaction of the viral envelope with the CD4 receptor found on human
       lymphocytes and other cells is utilized by free virus as a route of cell
       entry and also is involved in the direct cell-to-cell spread of the
       virus. A variety of recombinant molecular technologies have been used to
       isolate and characterise the various proteins which function as these
       key molecular targets of viral growth and development. Specific assays
       have been developed utilizing these proteins in order to 1) Screen
       synthetic and natural products and identify potential anti-viral
       compounds, and 2) Test drugs designed to be inhibitory based on either
       a) the characterisation and elucidation of mechanism of action of the
       target or b) on the structure of compounds discovered by screen. The
       results obtained to date and the future perspectives for using these
       molecular targeted approaches will be described and discussed.
 DE    Antiviral Agents/*THERAPEUTIC USE  DNA
       Nucleotidyltransferases/ANTAGONISTS & INHIB  Gene Expression Regulation,
       Viral/DRUG EFFECTS/GENETICS  Gene Products, rev/ANTAGONISTS &
       INHIB/GENETICS  Gene Products, tat/ANTAGONISTS & INHIB/GENETICS  Human
       HIV/*DRUG EFFECTS/GENETICS  HIV Infections/*DRUG THERAPY/MICROBIOLOGY
       HIV Protease Inhibitors/THERAPEUTIC USE  Reverse
       Transcriptase/ANTAGONISTS & INHIB  Virus Replication/DRUG
       EFFECTS/GENETICS  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

