dc.contributor.author | Lanzafame, Massimiliano | |
dc.contributor.author | Grampa, Valentina | |
dc.contributor.author | Vangelista, Luca | |
dc.date.accessioned | 2020-03-27T05:35:32Z | |
dc.date.available | 2020-03-27T05:35:32Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Secchi, M., Grampa, V., & Vangelista, L. (2018). Rational CCL5 mutagenesis integration in a lactobacilli platform generates extremely potent HIV-1 blockers. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-20300-9 | en_US |
dc.identifier.issn | 2045-2322 | |
dc.identifier.other | 10.1038/s41598-018-20300-9 | |
dc.identifier.uri | https://www.nature.com/articles/s41598-018-20300-9.pdf | |
dc.identifier.uri | http://nur.nu.edu.kz/handle/123456789/4553 | |
dc.description | https://www.nature.com/articles/s41598-018-20300-9 | en_US |
dc.description.abstract | Efforts to improve existing anti-HIV-1 therapies or develop preventatives have identified CCR5 as an important target and CCL5 as an ideal scaffold to sculpt potent HIV-1 entry inhibitors. We created novel human CCL5 variants that exhibit exceptional anti-HIV-1 features using recombinant lactobacilli (exploited for live microbicide development) as a screening platform. Protein design, expression and anti-HIV-1 activity flowed in iterative cycles, with a stepwise integration of successful mutations and refinement of an initial CCL5 mutant battery towards the generation of two ultimate CCL5 derivatives, a CCR5 agonist and a CCR5 antagonist with similar anti-HIV-1 potency. The CCR5 antagonist was tested in human macrophages and against primary R5 HIV-1 strains, exhibiting cross-clade low picomolar IC50 activity. Moreover, its successful combination with several HIV-1 inhibitors provided the ground for conceiving therapeutic and preventative anti-HIV-1 cocktails. Beyond HIV-1 infection, these CCL5 derivatives may now be tested against several inflammation-related pathologies where the CCL5:CCR5 axis plays a relevant role. | en_US |
dc.language.iso | en | en_US |
dc.publisher | Nature Research | en_US |
dc.relation.ispartofseries | Scientific Reports; | |
dc.rights | Attribution-NonCommercial-ShareAlike 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/3.0/us/ | * |
dc.subject | CCL5 | en_US |
dc.subject | mutagenes | en_US |
dc.subject | HIV-1 blockers | en_US |
dc.subject | Research Subject Categories::MEDICINE | en_US |
dc.subject | lactobacilli | en_US |
dc.title | Rational CCL5 mutagenesis integration in a lactobacilli platform generates extremely potent HIV-1 blockers | en_US |
dc.type | Article | en_US |
workflow.import.source | science |
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