{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:47:53Z","timestamp":1787593673628,"version":"build-2736575974"},"reference-count":46,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,9,2]],"date-time":"2019-09-02T00:00:00Z","timestamp":1567382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871694"],"award-info":[{"award-number":["81871694"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773447"],"award-info":[{"award-number":["81773447"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81561128006"],"award-info":[{"award-number":["81561128006"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21778074"],"award-info":[{"award-number":["21778074"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31470801"],"award-info":[{"award-number":["31470801"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81661148055"],"award-info":[{"award-number":["81661148055"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Major Project of the State Key Laboratory of Infectious Diseases Prevention and Control","award":["2011SKLID102"],"award-info":[{"award-number":["2011SKLID102"]}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2018ZX10101002"],"award-info":[{"award-number":["2018ZX10101002"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The clinical application of HIV fusion inhibitor, enfuvirtide (T20), was limited mainly because of its short half-life. Here we designed and synthesized two PEGylated C34 peptides, PEG2kC34 and PEG5kC34, with the PEG chain length of 2 and 5 kDa, respectively, and evaluated their anti-HIV-1 activity and mechanisms of action. We found that these two PEGylated peptides could bind to the HIV-1 peptide N36 to form high affinity complexes with high \u03b1-helicity. The peptides PEG2kC34 and PEG5kC34 effectively inhibited HIV-1 Env-mediated cell\u2013cell fusion with an effective concentration for 50% inhibition (EC50) of about 36 nM. They also inhibited infection of the laboratory-adapted HIV-1 strain NL4-3 with EC50 of about 4\u20135 nM, and against 47 HIV-1 clinical isolates circulating in China with mean EC50 of PEG2kC34 and PEG5kC34 of about 26 nM and 32 nM, respectively. The plasma half-life (t1\/2) of PEG2kC34 and PEG5kC34 was 2.6 h and 5.1 h, respectively, and the t1\/2 of PEGylated C34 was about 2.4-fold and 4.6-fold longer than C34 (~1.1 h), respectively. These findings suggest that PEGylated C34 with broad-spectrum anti-HIV-1 activity and prolonged half-life can be further developed as a peptide fusion inhibitor-based long-acting anti-HIV drug for clinical use to treat HIV-infected patients who have failed to respond to current anti-retrovirus drugs.<\/jats:p>","DOI":"10.3390\/v11090811","type":"journal-article","created":{"date-parts":[[2019,9,3]],"date-time":"2019-09-03T03:06:14Z","timestamp":1567479974000},"page":"811","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Long-Acting HIV-1 Fusion Inhibitory Peptides and their Mechanisms of Action"],"prefix":"10.3390","volume":"11","author":[{"given":"Chen","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS\/STD Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuihong","family":"Cheng","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS\/STD Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibo","family":"Ding","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS\/STD Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Chong","sequence":"additional","affiliation":[{"name":"MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology and Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xing","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS\/STD Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8283-7135","authenticated-orcid":false,"given":"Shibo","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), School of Basic Medical Sciences, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuebing","family":"Li","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS\/STD Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1080\/14728214.2018.1474202","article-title":"Emerging reverse transcriptase inhibitors for HIV-1 infection","volume":"23","author":"Rai","year":"2018","journal-title":"Expert Opin. 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