{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:31:34Z","timestamp":1777433494785,"version":"3.51.4"},"reference-count":42,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T00:00:00Z","timestamp":1667174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union\u2019s Framework Program 7","doi-asserted-by":"publisher","award":["242135"],"award-info":[{"award-number":["242135"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union\u2019s Framework Program 7","doi-asserted-by":"publisher","award":["021220FD2551"],"award-info":[{"award-number":["021220FD2551"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012632","name":"Nazarbayev Universit","doi-asserted-by":"publisher","award":["242135"],"award-info":[{"award-number":["242135"]}],"id":[{"id":"10.13039\/501100012632","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012632","name":"Nazarbayev Universit","doi-asserted-by":"publisher","award":["021220FD2551"],"award-info":[{"award-number":["021220FD2551"]}],"id":[{"id":"10.13039\/501100012632","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>With the aim of rationally devising a refined and potent HIV-1 blocker, the cDNA of CCL5 5p12 5m, an extremely potent CCR5 antagonist, was fused to that of C37, a gp41-targeted fusion inhibitor. The resulting CCL5 5p12 5m-C37 fusion protein was expressed in E. coli and proved to be capable of inhibiting R5 HIV-1 strains with low to sub-picomolar IC50, maintaining its antagonism toward CCR5. In addition, CCL5 5p12 5m-C37 inhibits R5\/X4 and X4 HIV-1 strains in the picomolar concentration range. The combination of CCL5 5p12 5m-C37 with tenofovir (TDF) exhibited a synergic effect, promoting this antiviral cocktail. Interestingly, a CCR5-targeted combination of maraviroc (MVC) with CCL5 5p12 5m-C37 led to a synergic effect that could be explained by an extensive engagement of different CCR5 conformational populations. Within the mechanism of HIV-1 entry, the CCL5 5p12 5m-C37 chimera may fit as a powerful blocker in several instances. In its possible consideration for systemic therapy or pre-exposure prophylaxis, this protein design represents an interesting lead in the combat of HIV-1 infection.<\/jats:p>","DOI":"10.3390\/v14112415","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T03:44:17Z","timestamp":1667360657000},"page":"2415","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Rational Engineering of a Sub-Picomolar HIV-1 Blocker"],"prefix":"10.3390","volume":"14","author":[{"given":"Massimiliano","family":"Secchi","sequence":"first","affiliation":[{"name":"Protein Engineering and Therapeutics Group, Department of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, 20132 Milan, Italy"},{"name":"DNA Enzymology and Molecular Virology Unit, Institute of Molecular Genetics, National Research Council, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0764-5031","authenticated-orcid":false,"given":"Luca","family":"Vangelista","sequence":"additional","affiliation":[{"name":"Protein Engineering and Therapeutics Group, Department of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, 20132 Milan, Italy"},{"name":"Department of Biomedical Sciences, School of Medicine, Nazarbayev University, Nur-Sultan 010000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"816515","DOI":"10.3389\/fimmu.2021.816515","article-title":"Targeting CCR5 as a component of an HIV-1 therapeutic strategy","volume":"12","author":"Mohamed","year":"2022","journal-title":"Front. 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