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Title: SRR-SB3, a disulfide-containing macrolide that inhibits a late stage of the replicative cycle of human immunodeficiency virus
Authors: Witvrouw, Myriam ×
Balzarini, Jan
Pannecouque, Christophe
Jhaumeer-Laulloo, S
Esté, J A
Schols, Dominique
Cherepanov, P
Schmit, J C
Debyser, Zeger
Vandamme, Anne-Mieke
Desmyter, Jan
Ramadas, S R
De Clercq, Erik #
Issue Date: Feb-1997
Series Title: Antimicrobial Agents and Chemotherapy vol:41 issue:2 pages:262-268
Abstract: From a series of macrocyclic diamides possessing the disulfide linkage, only SRR-SB3, a compound that complexes with zinc, was found to inhibit human immunodeficiency virus type 1 (HIV-1; strain IIIB) replication at a concentration of 1.8 to 6.5 micrograms/ml in MT-4, CEM, and peripheral blood mononuclear cells. SRR-SB3 was toxic to MT-4 cells at a concentration of 15.9 micrograms/ml, resulting in a selectivity index of 9 in these cells. This macrolide was also effective against various other HIV-1 strains, including clinical isolates and HIV-1 strains resistant to protease inhibitors and nucleoside and nonnucleoside reverse transcriptase inhibitors. It was also active against various HIV-2 strains, simian immunodeficiency virus (strain MAC251), and Moloney murine sarcoma virus, but not against viruses other than retroviruses. In addition, the compound was found to inhibit chronic HIV-1 infections in vitro. The compound in combination with other antiviral agents, such as zidovudine, zalcitabine, and stavudine, showed an effect that was between additive and synergistic. Time-of-addition experiments indicated that SRR-SB3 acts at a late stage of the HIV-1 replicative cycle.
ISSN: 0066-4804
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
Laboratory of Clinical and Epidemiological Virology (Rega Institute)
Molecular Virology and Gene Therapy
× corresponding author
# (joint) last author

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