Derivatives of MOPS : promising scaffolds for SARS coronaviruses Macro domain‐targeted inhibition
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| Formato: | Artículo Open Access |
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Wiley
2025
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| _version_ | 1867004657912512512 |
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| author | Oney Ortega Granda Karine Alvarez Benjamin Morin Bruno Canard François Ferron Nadia Rabah |
| author_facet | Oney Ortega Granda Karine Alvarez Benjamin Morin Bruno Canard François Ferron Nadia Rabah Oney Ortega Granda Karine Alvarez Benjamin Morin Bruno Canard François Ferron Nadia Rabah |
| collection | Wiley Open Access |
| contents | Derivatives of MOPS : promising scaffolds for SARS coronaviruses Macro domain‐targeted inhibition Oney Ortega Granda Karine Alvarez Benjamin Morin Bruno Canard François Ferron Nadia Rabah The FEBS Journal The severe acute respiratory syndrome coronavirus (SARS‐CoV/CoV‐2) genome encodes 16 non‐structural proteins (nsps), which coordinate cell remodeling, virus replication and participate in viral evasion. Notably, nsp3 contains a protein module termed Macro domain, which carries IFN antagonist activity that interferes with host innate immunity response. This domain is able to bind and hydrolyze ADP‐ribose derivatives. This activity is correlated to viral escape and thus makes Macro domains a valuable therapeutic target. In the present paper, we report a SARS‐CoV Macro domain structure in complex with a MOPS molecule. Based on our structural data, molecular docking was performed on a set of MOPS analogs in the ADP‐ribose binding pocket. We present an ELISA‐based assay to select hits based on the inhibition of recombinant SARS‐CoV/CoV‐2 Macro domain‐ADP‐ribose complex formation. Among the tested analogs, MOPSO and CAPSO are the more efficient in inhibiting ADP‐ribose‐binding. Structural analysis of these molecules in the ADP‐ribose pocket reveals potential interactions with amino acid residues involved in the coordination of ADP‐ribose. Overall, these findings suggest that MOPSO and CAPSO bear potential to be used as a scaffold for the design of Macro domain‐specific inhibitors. 10.1111/febs.70039 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| doi_str_mv | 10.1111/febs.70039 |
| format | Artículo Open Access |
| id | wiley_oa_10_1111_febs_70039 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Derivatives of MOPS : promising scaffolds for SARS coronaviruses Macro domain‐targeted inhibition Oney Ortega Granda Karine Alvarez Benjamin Morin Bruno Canard François Ferron Nadia Rabah The FEBS Journal Derivatives of MOPS : promising scaffolds for SARS coronaviruses Macro domain‐targeted inhibition Oney Ortega Granda Karine Alvarez Benjamin Morin Bruno Canard François Ferron Nadia Rabah The FEBS Journal The severe acute respiratory syndrome coronavirus (SARS‐CoV/CoV‐2) genome encodes 16 non‐structural proteins (nsps), which coordinate cell remodeling, virus replication and participate in viral evasion. Notably, nsp3 contains a protein module termed Macro domain, which carries IFN antagonist activity that interferes with host innate immunity response. This domain is able to bind and hydrolyze ADP‐ribose derivatives. This activity is correlated to viral escape and thus makes Macro domains a valuable therapeutic target. In the present paper, we report a SARS‐CoV Macro domain structure in complex with a MOPS molecule. Based on our structural data, molecular docking was performed on a set of MOPS analogs in the ADP‐ribose binding pocket. We present an ELISA‐based assay to select hits based on the inhibition of recombinant SARS‐CoV/CoV‐2 Macro domain‐ADP‐ribose complex formation. Among the tested analogs, MOPSO and CAPSO are the more efficient in inhibiting ADP‐ribose‐binding. Structural analysis of these molecules in the ADP‐ribose pocket reveals potential interactions with amino acid residues involved in the coordination of ADP‐ribose. Overall, these findings suggest that MOPSO and CAPSO bear potential to be used as a scaffold for the design of Macro domain‐specific inhibitors. 10.1111/febs.70039 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| title | Derivatives of MOPS : promising scaffolds for SARS coronaviruses Macro domain‐targeted inhibition |
| topic | The FEBS Journal |
| url | https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.70039 |