Aptamer-Hytac Chimeras for Targeted Degradation of SARS-CoV-2 Spike-1

Autor: Carme Fàbrega, Núria Gallisà-Suñé, Alice Zuin, Juan Sebastián Ruíz, Bernat Coll-Martínez, Gemma Fabriàs, Ramon Eritja, Bernat Crosas
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Cells, Vol 13, Iss 21, p 1767 (2024)
Druh dokumentu: article
ISSN: 2073-4409
DOI: 10.3390/cells13211767
Popis: The development of novel tools to tackle viral processes has become a central focus in global health, during the COVID-19 pandemic. The spike protein is currently one of the main SARS-CoV-2 targets, owing to its key roles in infectivity and virion formation. In this context, exploring innovative strategies to block the activity of essential factors of SARS-CoV-2, such as spike proteins, will strengthen the capacity to respond to current and future threats. In the present work, we developed and tested novel bispecific molecules that encompass: (i) oligonucleotide aptamers S901 and S702, which bind to the spike protein through its S1 domain, and (ii) hydrophobic tags, such as adamantane and tert-butyl-carbamate-based ligands. Hydrophobic tags have the capacity to trigger the degradation of targets recruited in the context of a proteolytic chimera by activating quality control pathways. We observed that S901-adamantyl conjugates promote the degradation of the S1 spike domain, stably expressed in human cells by genomic insertion. These results highlight the suitability of aptamers as target-recognition molecules and the robustness of protein quality control pathways triggered by hydrophobic signals, and place aptamer-Hytacs as promising tools for counteracting coronavirus progression in human cells.
Databáze: Directory of Open Access Journals
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