Document 0449
 DOCN  M9590449
 TI    Inhibition of human immunodeficiency virus replication by
       nonimmunosuppressive analogs of cyclosporin A.
 DT    9509
 AU    Bartz SR; Hohenwalter E; Hu MK; Rich DH; Malkovsky M; Department of
       Medical Microbiology and Immunology, University of; Wisconsin, Madison
       53706, USA.
 SO    Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5381-5. Unique Identifier :
       AIDSLINE MED/95296314
 AB    Analogs of the immunosuppressive cyclic undecapeptide cyclosporin A
       (CsA) with substitutions in positions 1, 4, 6, and/or 11 were rationally
       designed to possess substantially diminished or no immunosuppressive
       activity. When these compounds were assayed for their capacity to
       interfere with the replication of human immunodeficiency virus, some
       displayed a potent antiviral activity in newly infected cells. However,
       only CsA could interfere with virus replication in persistently infected
       cells. One CsA analog with antiviral activity costimulated the
       phytohemagglutinin-induced production of interleukin 2 by human
       lymphocytes. Human immunodeficiency virus particles from drug-exposed
       cells showed lower infectivity than virions from untreated cells. Thus,
       these nonimmunosuppressive analogs of CsA constitute a promising class
       of lead compounds to develop drugs for effective treatment of the
       acquired immunodeficiency syndrome.
 DE    Antiviral Agents/*PHARMACOLOGY  Cell Line  Cyclosporine/PHARMACOLOGY
       Cyclosporins/CHEMISTRY/*PHARMACOLOGY  Drug Design  Human  HIV/*DRUG
       EFFECTS/PHYSIOLOGY/PATHOGENICITY  Interleukin-2/BIOSYNTHESIS  Lymphocyte
       Transformation/DRUG EFFECTS  Lymphocytes/IMMUNOLOGY  Models, Molecular
       Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Virus
       Replication/*DRUG EFFECTS  JOURNAL ARTICLE

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