Aptamer-Hytac Chimeras for Targeted Degradation of SARS-CoV-2 Spike-1
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 str...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-10-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/13/21/1767 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846173499269316608 |
|---|---|
| author | Carme Fàbrega Núria Gallisà-Suñé Alice Zuin Juan Sebastián Ruíz Bernat Coll-Martínez Gemma Fabriàs Ramon Eritja Bernat Crosas |
| author_facet | Carme Fàbrega Núria Gallisà-Suñé Alice Zuin Juan Sebastián Ruíz Bernat Coll-Martínez Gemma Fabriàs Ramon Eritja Bernat Crosas |
| author_sort | Carme Fàbrega |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-00d1b154c83841d2a3310f94588a1da2 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-00d1b154c83841d2a3310f94588a1da22024-11-08T14:34:26ZengMDPI AGCells2073-44092024-10-011321176710.3390/cells13211767Aptamer-Hytac Chimeras for Targeted Degradation of SARS-CoV-2 Spike-1Carme Fàbrega0Núria Gallisà-Suñé1Alice Zuin2Juan Sebastián Ruíz3Bernat Coll-Martínez4Gemma Fabriàs5Ramon Eritja6Bernat Crosas7Department of Surfactants and Nanobiotechnology, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Jordi Girona 18, 08034 Barcelona, SpainProteasome Regulation Lab, Department of Cells and Tissues, Molecular Biology Institute of Barcelona (IBMB-CSIC), Baldiri i Reixac 4, 08028 Barcelona, SpainProteasome Regulation Lab, Department of Cells and Tissues, Molecular Biology Institute of Barcelona (IBMB-CSIC), Baldiri i Reixac 4, 08028 Barcelona, SpainLincbiotech SL, Avenida do Mestre Mateo, 2, 15706 Santiago de Compostela, SpainProteasome Regulation Lab, Department of Cells and Tissues, Molecular Biology Institute of Barcelona (IBMB-CSIC), Baldiri i Reixac 4, 08028 Barcelona, SpainDepartment of Biological Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Jordi Girona 18, 08034 Barcelona, SpainDepartment of Surfactants and Nanobiotechnology, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Jordi Girona 18, 08034 Barcelona, SpainProteasome Regulation Lab, Department of Cells and Tissues, Molecular Biology Institute of Barcelona (IBMB-CSIC), Baldiri i Reixac 4, 08028 Barcelona, SpainThe 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.https://www.mdpi.com/2073-4409/13/21/1767coronavirusSARS-CoV-2spike proteinaptameroligonucleotideadamantyl |
| spellingShingle | Carme Fàbrega Núria Gallisà-Suñé Alice Zuin Juan Sebastián Ruíz Bernat Coll-Martínez Gemma Fabriàs Ramon Eritja Bernat Crosas Aptamer-Hytac Chimeras for Targeted Degradation of SARS-CoV-2 Spike-1 Cells coronavirus SARS-CoV-2 spike protein aptamer oligonucleotide adamantyl |
| title | Aptamer-Hytac Chimeras for Targeted Degradation of SARS-CoV-2 Spike-1 |
| title_full | Aptamer-Hytac Chimeras for Targeted Degradation of SARS-CoV-2 Spike-1 |
| title_fullStr | Aptamer-Hytac Chimeras for Targeted Degradation of SARS-CoV-2 Spike-1 |
| title_full_unstemmed | Aptamer-Hytac Chimeras for Targeted Degradation of SARS-CoV-2 Spike-1 |
| title_short | Aptamer-Hytac Chimeras for Targeted Degradation of SARS-CoV-2 Spike-1 |
| title_sort | aptamer hytac chimeras for targeted degradation of sars cov 2 spike 1 |
| topic | coronavirus SARS-CoV-2 spike protein aptamer oligonucleotide adamantyl |
| url | https://www.mdpi.com/2073-4409/13/21/1767 |
| work_keys_str_mv | AT carmefabrega aptamerhytacchimerasfortargeteddegradationofsarscov2spike1 AT nuriagallisasune aptamerhytacchimerasfortargeteddegradationofsarscov2spike1 AT alicezuin aptamerhytacchimerasfortargeteddegradationofsarscov2spike1 AT juansebastianruiz aptamerhytacchimerasfortargeteddegradationofsarscov2spike1 AT bernatcollmartinez aptamerhytacchimerasfortargeteddegradationofsarscov2spike1 AT gemmafabrias aptamerhytacchimerasfortargeteddegradationofsarscov2spike1 AT ramoneritja aptamerhytacchimerasfortargeteddegradationofsarscov2spike1 AT bernatcrosas aptamerhytacchimerasfortargeteddegradationofsarscov2spike1 |