tetano
Editor, Senior Moderator
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[SUP] 1 2 [/SUP], Núria Gallisà-Suñé[SUP] 3 [/SUP], Alice Zuin[SUP] 3 [/SUP], Juan Sebastián Ruíz[SUP] 4 [/SUP], Bernat Coll-Martínez[SUP] 3 [/SUP], Gemma Fabriàs[SUP] 5 [/SUP], Ramon Eritja[SUP] 1 2 [/SUP], Bernat Crosas[SUP] 3 [/SUP]
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[SUP] 1 2 [/SUP], Núria Gallisà-Suñé[SUP] 3 [/SUP], Alice Zuin[SUP] 3 [/SUP], Juan Sebastián Ruíz[SUP] 4 [/SUP], Bernat Coll-Martínez[SUP] 3 [/SUP], Gemma Fabriàs[SUP] 5 [/SUP], Ramon Eritja[SUP] 1 2 [/SUP], Bernat Crosas[SUP] 3 [/SUP]
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).