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| Autori principali: | , , , , , , , |
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| Natura: | Artículo científico |
| Lingua: | en |
| Pubblicazione: |
Pharmaceuticals (Basel, Switzerland)
2026
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| Accesso online: | https://pubmed.ncbi.nlm.nih.gov/41754834/ |
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| _version_ | 1868266079686492161 |
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| author | Dalisay, Doralyn S Mateo, Jomari C Teodosio, Jade Joshua R de Guzman, Leighiara S Marcial, Neaven Bon Joy M Caspe, Dion Paul C Balida, Lex Aliko P Jamal, Jamia Azdina |
| author_facet | Dalisay, Doralyn S Mateo, Jomari C Teodosio, Jade Joshua R de Guzman, Leighiara S Marcial, Neaven Bon Joy M Caspe, Dion Paul C Balida, Lex Aliko P Jamal, Jamia Azdina Dalisay, Doralyn S Mateo, Jomari C Teodosio, Jade Joshua R de Guzman, Leighiara S Marcial, Neaven Bon Joy M Caspe, Dion Paul C Balida, Lex Aliko P Jamal, Jamia Azdina |
| collection | PubMed - marine biology |
| contents | Marine -Derived Lipids Inhibit SARS-CoV-2 3CLpro Through In Vitro and Predicted Multi-Site Binding Mechanisms. Dalisay, Doralyn S Mateo, Jomari C Teodosio, Jade Joshua R de Guzman, Leighiara S Marcial, Neaven Bon Joy M Caspe, Dion Paul C Balida, Lex Aliko P Jamal, Jamia Azdina : The SARS-CoV-2 3CLpro is essential for viral replication and an attractive target for antiviral intervention. While most strategies target the catalytic site, recent studies suggest that the dimerization interface and cryptic allosteric pockets offer alternative mechanisms for inhibition. : This study investigated lipid metabolites from the marine sediment-derived sp. DSD454 as potential multi-site 3CLpro inhibitors. : Metabolites were extracted from cultured biomass and characterized using LCMS-QTOF, MS/MS (LCMS-TQ), and H NMR, with identities confirmed against authentic standards. 3CLpro inhibition was assessed using a FRET-based assay, and ligand-protein interactions were evaluated through molecular docking and MM/GBSA calculations. Lipid content and comparative lipidomic signatures were examined across bioactive strains through LCMS-TQ and BODIPY 493/503 staining. : Palmitoleic and linoleic acids were identified as major constituents and inhibited SARS-CoV-2 3CLpro with IC values of 1.59 µg/mL (6.25 µM) and 5.29 µg/mL (18.88 µM). Molecular docking predicted that both fatty acids bind not only to the catalytic site but also to the dimerization interface and cryptic allosteric pocket. Additional lipids, including 9-heptadecenoic acid, linolenic acid, 9-HODE, and monoacylglycerols such as aggrecerides A-C and glyceryl-based lipids, showed similarly favorable multi-site binding profiles. sp. DSD454 also exhibited substantial lipid accumulation (~63% of crude extract). Across bioactive strains, a conserved lipid signature correlated strongly with 3CLpro inhibition. : This study highlights the potential of microbial lipids as promising scaffolds for developing catalytic and allosteric SARS-CoV-2 3CLpro inhibitors and underscore marine as a valuable source of structurally simple yet mechanistically versatile antiviral metabolites. |
| format | Artículo científico |
| id | pubmed_41754834 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | Pharmaceuticals (Basel, Switzerland) |
| record_format | pubmed |
| spellingShingle | Marine -Derived Lipids Inhibit SARS-CoV-2 3CLpro Through In Vitro and Predicted Multi-Site Binding Mechanisms. Dalisay, Doralyn S Mateo, Jomari C Teodosio, Jade Joshua R de Guzman, Leighiara S Marcial, Neaven Bon Joy M Caspe, Dion Paul C Balida, Lex Aliko P Jamal, Jamia Azdina Marine -Derived Lipids Inhibit SARS-CoV-2 3CLpro Through In Vitro and Predicted Multi-Site Binding Mechanisms. Dalisay, Doralyn S Mateo, Jomari C Teodosio, Jade Joshua R de Guzman, Leighiara S Marcial, Neaven Bon Joy M Caspe, Dion Paul C Balida, Lex Aliko P Jamal, Jamia Azdina : The SARS-CoV-2 3CLpro is essential for viral replication and an attractive target for antiviral intervention. While most strategies target the catalytic site, recent studies suggest that the dimerization interface and cryptic allosteric pockets offer alternative mechanisms for inhibition. : This study investigated lipid metabolites from the marine sediment-derived sp. DSD454 as potential multi-site 3CLpro inhibitors. : Metabolites were extracted from cultured biomass and characterized using LCMS-QTOF, MS/MS (LCMS-TQ), and H NMR, with identities confirmed against authentic standards. 3CLpro inhibition was assessed using a FRET-based assay, and ligand-protein interactions were evaluated through molecular docking and MM/GBSA calculations. Lipid content and comparative lipidomic signatures were examined across bioactive strains through LCMS-TQ and BODIPY 493/503 staining. : Palmitoleic and linoleic acids were identified as major constituents and inhibited SARS-CoV-2 3CLpro with IC values of 1.59 µg/mL (6.25 µM) and 5.29 µg/mL (18.88 µM). Molecular docking predicted that both fatty acids bind not only to the catalytic site but also to the dimerization interface and cryptic allosteric pocket. Additional lipids, including 9-heptadecenoic acid, linolenic acid, 9-HODE, and monoacylglycerols such as aggrecerides A-C and glyceryl-based lipids, showed similarly favorable multi-site binding profiles. sp. DSD454 also exhibited substantial lipid accumulation (~63% of crude extract). Across bioactive strains, a conserved lipid signature correlated strongly with 3CLpro inhibition. : This study highlights the potential of microbial lipids as promising scaffolds for developing catalytic and allosteric SARS-CoV-2 3CLpro inhibitors and underscore marine as a valuable source of structurally simple yet mechanistically versatile antiviral metabolites. |
| title | Marine -Derived Lipids Inhibit SARS-CoV-2 3CLpro Through In Vitro and Predicted Multi-Site Binding Mechanisms. |
| url | https://pubmed.ncbi.nlm.nih.gov/41754834/ |