{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T17:49:42Z","timestamp":1761155382600},"reference-count":57,"publisher":"American Society for Microbiology","issue":"18","license":[{"start":{"date-parts":[[2010,9,15]],"date-time":"2010-09-15T00:00:00Z","timestamp":1284508800000},"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":[[2010,9,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Human immunodeficiency virus type 1 (HIV-1) gp41 plays a critical role in the viral fusion process, and its N- and C-terminal heptad repeat domains serve as important targets for developing anti-HIV-1 drugs, like T-20 (generic name, enfuvirtide; brand name, Fuzeon). Here, we conducted a yeast two-hybrid screening on a human bone marrow cDNA library using the recombinant soluble gp41 ectodomain as the bait and identified a novel gp41 core-binding molecule, designated P20. P20 showed no homology with a current HIV fusion inhibitor, T-20, but had sequence homology to a human protein, troponin I type 3 interacting kinase (TNNI3K)-like protein. While it could bind to the six-helix bundle core structure formed by the N- and C-terminal heptad repeats, P20 did not interrupt the formation of the six-helix bundle. P20 was effective in blocking HIV-1 Env-mediated syncytium formation and inhibiting infection by a broad spectrum of HIV-1 strains with distinct subtypes and coreceptor tropism, while it was ineffective against other enveloped viruses, such as vesicular stomatitis virus and influenza A virus. P20 exhibited no significant cytotoxicity to the CD4\n            <jats:sup>+<\/jats:sup>\n            cells that were used for testing antiviral activity. Among the 11 P20 mutants, four analogous peptides with a common motif (WGRLEGRRT) exhibited significantly reduced anti-HIV-1 activity, suggesting that this region is the critical active site of P20. Therefore, this peptide can be used as a lead for developing novel HIV fusion inhibitors and as a probe for studying the membrane-fusogenic mechanism of HIV.\n          <\/jats:p>","DOI":"10.1128\/jvi.00644-10","type":"journal-article","created":{"date-parts":[[2010,7,1]],"date-time":"2010-07-01T02:14:51Z","timestamp":1277950491000},"page":"9359-9368","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Identification of a gp41 Core-Binding Molecule with Homologous Sequence of Human TNNI3K-Like Protein as a Novel Human Immunodeficiency Virus Type 1 Entry Inhibitor"],"prefix":"10.1128","volume":"84","author":[{"given":"Yun","family":"Zhu","sequence":"first","affiliation":[{"name":"Laboratory of Immunology, School of Life Sciences, Tsinghua University, Beijing Key Laboratory for Protein Therapeutics, Protein Science Laboratory of MOE, Beijing, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Lu","sequence":"additional","affiliation":[{"name":"Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liling","family":"Xu","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, School of Life Sciences, Tsinghua University, Beijing Key Laboratory for Protein Therapeutics, Protein Science Laboratory of MOE, Beijing, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hengwen","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, School of Life Sciences, Tsinghua University, Beijing Key Laboratory for Protein Therapeutics, Protein Science Laboratory of MOE, Beijing, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shibo","family":"Jiang","sequence":"additional","affiliation":[{"name":"Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-Hua","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, School of Life Sciences, Tsinghua University, Beijing Key Laboratory for Protein Therapeutics, Protein Science Laboratory of MOE, Beijing, People's Republic of 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