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Cells
. 2024 Oct 25;13(21):1767.
doi: 10.3390/cells13211767. Aptamer-Hytac Chimeras for Targeted Degradation of SARS-CoV-2 Spike-1
Carme Fàbrega 1 2 , Núria Gallisà-Suñé 3 , Alice Zuin 3 , Juan Sebastián Ruíz 4 , Bernat Coll-Martínez 3 , Gemma Fabriàs 5 , Ramon Eritja 1 2 , Bernat Crosas 3
Affiliations
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.
Keywords: SARS-CoV-2; adamantyl; aptamer; coronavirus; oligonucleotide; spike protein; targeted protein degradation; tert-butyl carbamate (Boc).
. 2024 Oct 25;13(21):1767.
doi: 10.3390/cells13211767. Aptamer-Hytac Chimeras for Targeted Degradation of SARS-CoV-2 Spike-1
Carme Fàbrega 1 2 , Núria Gallisà-Suñé 3 , Alice Zuin 3 , Juan Sebastián Ruíz 4 , Bernat Coll-Martínez 3 , Gemma Fabriàs 5 , Ramon Eritja 1 2 , Bernat Crosas 3
Affiliations
- PMID: 39513874
- DOI: 10.3390/cells13211767
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.
Keywords: SARS-CoV-2; adamantyl; aptamer; coronavirus; oligonucleotide; spike protein; targeted protein degradation; tert-butyl carbamate (Boc).