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  • Title: An inhibitor of the protease blocks maturation of human and simian immunodeficiency viruses and spread of infection.
    Author: Ashorn P, McQuade TJ, Thaisrivongs S, Tomasselli AG, Tarpley WG, Moss B.
    Journal: Proc Natl Acad Sci U S A; 1990 Oct; 87(19):7472-6. PubMed ID: 2217178.
    Abstract:
    The activity of the human immunodeficiency virus (HIV) protease is essential for processing of the gag-pol precursor proteins and maturation of infectious virions. We have prepared a peptidomimetic inhibitor, U-75875, that inhibited HIV-1 gag-pol protein processing in an essentially irreversible manner. Noninfectious virus particles produced in the presence of the drug contained gag precursors and were morphologically immature. In human peripheral blood mononuclear cells and in a continuous cell line, U-75875 completely blocked HIV replication; in the latter case, no spread occurred over a period of 4 weeks. U-75875, on a molar basis, was as potent as 3'-azido-3'-deoxythymidine in blocking HIV-1 replication in human lymphocytes and also inhibited HIV-2 and simian immunodeficiency virus proteases, demonstrating that it has broad activity. These results provide further evidence for the therapeutic potential of protease inhibitors in HIV infection.
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