{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T11:03:20Z","timestamp":1760267000941},"reference-count":33,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2010,4,1]],"date-time":"2010-04-01T00:00:00Z","timestamp":1270080000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Pradimicin S (PRM-S) is a highly water-soluble, negatively charged derivative of the antibiotic pradimicin A (PRM-A) in which the terminal xylose moiety has been replaced by 3-sulfated glucose. PRM-S does not prevent human immunodeficiency virus (HIV) adsorption on CD4\n            <jats:sup>+<\/jats:sup>\n            T cells, but it blocks virus entry into its target cells. It inhibits a wide variety of HIV-1 laboratory strains and clinical isolates, HIV-2, and simian immunodeficiency virus (SIV) in various cell culture systems (50% and 90% effective concentrations [EC\n            <jats:sub>50<\/jats:sub>\n            s and EC\n            <jats:sub>90<\/jats:sub>\n            s] invariably in the lower micromolar range). PRM-S inhibits syncytium formation between persistently HIV-1- and SIV-infected cells and uninfected CD4\n            <jats:sup>+<\/jats:sup>\n            T lymphocytes, and prevents dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)-mediated HIV-1 and SIV capture and subsequent virus transmission to CD4\n            <jats:sup>+<\/jats:sup>\n            T cells. Surface plasmon resonance (SPR) studies revealed that PRM-S strongly binds to gp120 in a Ca\n            <jats:sup>2+<\/jats:sup>\n            -dependent manner at an affinity constant (\n            <jats:italic>\n              K\n              <jats:sub>D<\/jats:sub>\n            <\/jats:italic>\n            ) in the higher nanomolar range. Its anti-HIV activity and HIV-1 gp120-binding properties can be dose-dependently reversed in the presence of an (\u03b1-1,2)mannose trimer. Dose-escalating exposure of HIV-1-infected cells to PRM-S eventually led to the isolation of mutant virus strains that had various deleted N-glycosylation sites in the envelope gp120 with a strong preference for the deletion of the high-mannose-type glycans. Genotypic resistance development occurred slowly, and significant phenotypic resistance occurred only after the sequential appearance of up to six mutations in gp120, pointing to a high genetic barrier of PRM-S. The antibiotic is nontoxic against a variety of cell lines, is not mitogenic, and does not induce cytokines and chemokines in peripheral blood mononuclear cells as determined by the Bio-Plex human cytokine 27-plex assay. It proved stable at high temperature and low pH. Therefore, PRM-S may qualify as a potential anti-HIV drug candidate for further (pre)clinical studies, including its microbicidal use.\n          <\/jats:p>","DOI":"10.1128\/aac.01347-09","type":"journal-article","created":{"date-parts":[[2010,1,5]],"date-time":"2010-01-05T02:10:30Z","timestamp":1262657430000},"page":"1425-1435","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":43,"title":["Pradimicin S, a Highly Soluble Nonpeptidic Small-Size Carbohydrate-Binding Antibiotic, Is an Anti-HIV Drug Lead for both Microbicidal and Systemic Use"],"prefix":"10.1128","volume":"54","author":[{"given":"Jan","family":"Balzarini","sequence":"first","affiliation":[{"name":"Rega Institute for Medical Research, K.U. Leuven, B-3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrien O.","family":"Franc\u0327ois","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, K.U. Leuven, B-3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristel","family":"Van Laethem","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, K.U. Leuven, B-3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart","family":"Hoorelbeke","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, K.U. Leuven, B-3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marleen","family":"Renders","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, K.U. 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