{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T04:53:34Z","timestamp":1768971214240,"version":"3.49.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2007,11,1]],"date-time":"2007-11-01T00:00:00Z","timestamp":1193875200000},"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":[[2007,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Despite the success of highly active antiretroviral therapy, the current emergence and spread of drug-resistant variants of human immunodeficiency virus (HIV) stress the need for new inhibitors with distinct properties. We designed, produced, and screened a library of compounds based on an original\n            <jats:sc>l<\/jats:sc>\n            -lysine scaffold for their potentials as HIV type 1 (HIV-1) protease inhibitors (PI). One candidate compound, PL-100, emerged as a specific and noncytotoxic PI that exhibited potent inhibition of HIV-1 protease and viral replication in vitro (\n            <jats:italic>\n              K\n              <jats:sub>i<\/jats:sub>\n            <\/jats:italic>\n            , \u223c36 pM, and 50% effective concentration [EC\n            <jats:sub>50<\/jats:sub>\n            ], \u223c16 nM, respectively). To confirm that PL-100 possessed a favorable resistance profile, we performed a cross-resistance study using a panel of 63 viral strains from PI-experienced patients selected for the presence of primary PI mutations known to confer resistance to multiple PIs now in clinical use. The results showed that PL-100 retained excellent antiviral activity against almost all of these PI-resistant viruses and that its performance in this regard was superior to those of atazanavir, amprenavir, indinavir, lopinavir, nelfinavir, and saquinavir. In almost every case, the increase in the EC\n            <jats:sub>50<\/jats:sub>\n            for PL-100 observed with viruses containing multiple mutations in protease was far less than that obtained with the other drugs tested. These data underscore the potential for PL-100 to be used in the treatment of drug-resistant HIV disease and argue for its further development.\n          <\/jats:p>","DOI":"10.1128\/aac.00149-07","type":"journal-article","created":{"date-parts":[[2007,7,17]],"date-time":"2007-07-17T00:41:17Z","timestamp":1184632877000},"page":"4036-4043","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["In Vitro Antiviral Activity and Cross-Resistance Profile of PL-100, a Novel Protease Inhibitor of Human Immunodeficiency Virus Type 1"],"prefix":"10.1128","volume":"51","author":[{"given":"Serge","family":"Dandache","sequence":"first","affiliation":[{"name":"Ambrilia Biopharma, Incorporated, Verdun, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy","family":"Se\u0301vigny","sequence":"additional","affiliation":[{"name":"Ambrilia Biopharma, Incorporated, Verdun, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jocelyn","family":"Yelle","sequence":"additional","affiliation":[{"name":"Ambrilia Biopharma, Incorporated, Verdun, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brent R.","family":"Stranix","sequence":"additional","affiliation":[{"name":"Ambrilia Biopharma, Incorporated, Verdun, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil","family":"Parkin","sequence":"additional","affiliation":[{"name":"Monogram Biosciences, South San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan M.","family":"Schapiro","sequence":"additional","affiliation":[{"name":"National Hemophilia Center, Tel Hashomer, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"Wainberg","sequence":"additional","affiliation":[{"name":"McGill University AIDS Centre, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinzi J.","family":"Wu","sequence":"additional","affiliation":[{"name":"Ambrilia Biopharma, Incorporated, Verdun, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.59.2.284-291.1986"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200107270-00006"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.5.2472-2482.2006"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/374569a0"},{"key":"e_1_3_2_6_2","first-page":"78","year":"1997","unstructured":"Division of AIDS, National Institute of Allergy and Infectious Diseases. 1997. 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