{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T21:09:22Z","timestamp":1781903362813,"version":"3.54.5"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"13","license":[{"start":{"date-parts":[[2008,7,1]],"date-time":"2008-07-01T00:00:00Z","timestamp":1214870400000},"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":["J Virol"],"published-print":{"date-parts":[[2008,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Human immunodeficiency virus type 1 (HIV-1) entry into the host cell involves a cascade of events and currently represents one of most attractive targets in the search for new antiviral drugs. The fusion-active gp41 core structure is a stable six-helix bundle (6-HB) folded by its trimeric N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR). Peptides derived from the CHR region of HIV-1 gp41 are potent fusion inhibitors that target the NHR to block viral and cellular membrane fusion in a dominant negative fashion. However, all CHR peptides reported to date are derived primarily from residues 628 to 673 of gp41; little attention has been paid to the upstream sequence of the pocket binding domain (PBD) in the CHR. Here, we have identified a motif (<jats:sup>621<\/jats:sup>QIWNNMT<jats:sup>627<\/jats:sup>) located at the upstream region of the gp41 CHR, immediately adjacent to the PBD (<jats:sup>628<\/jats:sup>WMEWEREI<jats:sup>635<\/jats:sup>). Biophysical characterization demonstrated that this motif is critical for the stabilization of the gp41 6-HB core. The peptide CP621-652, containing the<jats:sup>621<\/jats:sup>QIWNNMT<jats:sup>627<\/jats:sup>motif, was able to interact with T21, a counterpart peptide derived from the NHR, to form a typical 6-HB structure with a high thermostability (thermal unfolding transition [<jats:italic>T<\/jats:italic><jats:sub><jats:italic>m<\/jats:italic><\/jats:sub>] value of 82\u00b0C). In contrast, the 6-HB formed by the peptides N36 and C34, which has been considered to be a core structure of the fusion-active gp41, had a<jats:italic>T<\/jats:italic><jats:sub><jats:italic>m<\/jats:italic><\/jats:sub>of 64\u00b0C. Different from T-20 (brand name Fuseon), which is the first and only HIV-1 fusion inhibitor approved for clinical use, CP621-652 could efficiently block 6-HB formation in a dose-dependent manner. Significantly, CP621-652 had potent inhibitory activity against HIV-1-mediated cell-cell fusion and infection, especially against T-20- and C34-resistant virus. Therefore, our works provide important information for understanding the core structure of the fusion-active gp41 and for designing novel anti-HIV peptides.<\/jats:p>","DOI":"10.1128\/jvi.00319-08","type":"journal-article","created":{"date-parts":[[2008,4,17]],"date-time":"2008-04-17T01:10:29Z","timestamp":1208394629000},"page":"6349-6358","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":79,"title":["Identification of a Critical Motif for the Human Immunodeficiency Virus Type 1 (HIV-1) gp41 Core Structure: Implications for Designing Novel Anti-HIV Fusion Inhibitors"],"prefix":"10.1128","volume":"82","author":[{"given":"Yuxian","family":"He","sequence":"first","affiliation":[{"name":"AIDS Research Center, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"},{"name":"Lindsley F. 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