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Representative DNA gyrase inhibitors, eukaryotic topoisomerase I and II inhibitors and DNA cleaving or binding compounds were screened for their activity against human immunodeficiency virus (HIV) replication in MT-2 cells, with the HIV supercoiled DNA form as the proposed target. Of 17 compounds, only the DNA gyrase inhibitor coumermycin A1 was active. This inhibition was observed for two HIV isolates in both MT-2 cells and peripheral blood leucocytes, and could not be attributed to cytotoxicity. Coumermycin A1 did not inhibit HIV reverse transcriptase activity in an in vitro assay at concentrations that inhibited HIV replication in infected cells; its precise mechanism of action remains to be elucidated.
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