A multi-targeted approach to identify potential flavonoids against three targets in the SARS-CoV-2 life cycle
<p dir="ltr">The advent and persistence of the Severe Acute Respiratory Syndrome Coronavirus – 2 (SARS-CoV-2)-induced Coronavirus Disease (COVID-19) pandemic since December 2019 has created the largest public health emergency in over a century. Despite the administration of multiple...
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| مؤلفون آخرون: | , , , , , |
| منشور في: |
2022
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إضافة وسم
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| _version_ | 1864513554091081728 |
|---|---|
| author | Sanjay Kumar (8853) |
| author2 | Pradipta Paul (12628162) Pardeep Yadav (17128870) Ridhima Kaul (12485902) S.S. Maitra (17128873) Saurabh Kumar Jha (16451348) Ali Chaari (827168) |
| author2_role | author author author author author author |
| author_facet | Sanjay Kumar (8853) Pradipta Paul (12628162) Pardeep Yadav (17128870) Ridhima Kaul (12485902) S.S. Maitra (17128873) Saurabh Kumar Jha (16451348) Ali Chaari (827168) |
| author_role | author |
| dc.creator.none.fl_str_mv | Sanjay Kumar (8853) Pradipta Paul (12628162) Pardeep Yadav (17128870) Ridhima Kaul (12485902) S.S. Maitra (17128873) Saurabh Kumar Jha (16451348) Ali Chaari (827168) |
| dc.date.none.fl_str_mv | 2022-03-01T00:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1016/j.compbiomed.2022.105231 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/A_multi-targeted_approach_to_identify_potential_flavonoids_against_three_targets_in_the_SARS-CoV-2_life_cycle/24288028 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Cardiovascular medicine and haematology Medical biochemistry and metabolomics Natural products COVID-19 Computational studies COVID-19 drug discovery Glycosylated flavonoids Hesperidin NaringinIn silico SARS-CoV-2 TMPRSS2 3CLpro PLpro |
| dc.title.none.fl_str_mv | A multi-targeted approach to identify potential flavonoids against three targets in the SARS-CoV-2 life cycle |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">The advent and persistence of the Severe Acute Respiratory Syndrome Coronavirus – 2 (SARS-CoV-2)-induced Coronavirus Disease (COVID-19) pandemic since December 2019 has created the largest public health emergency in over a century. Despite the administration of multiple vaccines across the globe, there continues to be a lack of approved efficacious non-prophylactic interventions for the disease. Flavonoids are a class of phytochemicals with historically established antiviral, anti-inflammatory and antioxidative properties that are effective against cancers, type 2 diabetes mellitus, and even other human coronaviruses. To identify the most promising bioactive flavonoids against the SARS-CoV-2, this article screened a virtual library of 46 bioactive flavonoids against three promising targets in the SARS-CoV-2 life cycle: human TMPRSS2 protein, 3CLpro, and PLpro. By examining the effects of glycosylation and other structural-activity relationships, the presence of sugar moiety in flavonoids significantly reduces its binding energy. It increases the solubility of flavonoids leading to reduced toxicity and higher bioavailability. Through protein-ligand contact profiling, it was concluded that naringin formed more hydrogen bonds with TMPRSS2 and 3CLpro.</p><p dir="ltr">In contrast, hesperidin formed a more significant number of hydrogen bonds with PLpro. These observations were complimented by the 100 ns molecular dynamics simulation and binding free energy analysis, which showed a considerable stability of docked bioflavonoids in the active site of SARS-CoV-2 target proteins. Finally, the binding affinity and stability of the selected docked complexes were compared with the reference ligands (camostat for TMPRSS2, GC376 for 3CLpro, and GRL0617 for PLpro) that strongly inhibit their respective SARS-COV-2 targets. Overall analysis revealed that the selected flavonoids could be potential therapeutic agents against SARS-CoV-2. Naringin showed better affinity and stability for TMPRSS2 and 3CLpro, whereas hesperidin showed a better binding relationship and stability for PLpro.</p><h2>Other Information</h2><p dir="ltr">Published in: Computers in Biology and Medicine<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.compbiomed.2022.105231" target="_blank">https://dx.doi.org/10.1016/j.compbiomed.2022.105231</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_7ca9c36ad3a69604874e8deb71c09042 |
| identifier_str_mv | 10.1016/j.compbiomed.2022.105231 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/24288028 |
| publishDate | 2022 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | A multi-targeted approach to identify potential flavonoids against three targets in the SARS-CoV-2 life cycleSanjay Kumar (8853)Pradipta Paul (12628162)Pardeep Yadav (17128870)Ridhima Kaul (12485902)S.S. Maitra (17128873)Saurabh Kumar Jha (16451348)Ali Chaari (827168)Biomedical and clinical sciencesCardiovascular medicine and haematologyMedical biochemistry and metabolomicsNatural productsCOVID-19Computational studiesCOVID-19 drug discoveryGlycosylated flavonoidsHesperidinNaringinIn silicoSARS-CoV-2TMPRSS23CLproPLpro<p dir="ltr">The advent and persistence of the Severe Acute Respiratory Syndrome Coronavirus – 2 (SARS-CoV-2)-induced Coronavirus Disease (COVID-19) pandemic since December 2019 has created the largest public health emergency in over a century. Despite the administration of multiple vaccines across the globe, there continues to be a lack of approved efficacious non-prophylactic interventions for the disease. Flavonoids are a class of phytochemicals with historically established antiviral, anti-inflammatory and antioxidative properties that are effective against cancers, type 2 diabetes mellitus, and even other human coronaviruses. To identify the most promising bioactive flavonoids against the SARS-CoV-2, this article screened a virtual library of 46 bioactive flavonoids against three promising targets in the SARS-CoV-2 life cycle: human TMPRSS2 protein, 3CLpro, and PLpro. By examining the effects of glycosylation and other structural-activity relationships, the presence of sugar moiety in flavonoids significantly reduces its binding energy. It increases the solubility of flavonoids leading to reduced toxicity and higher bioavailability. Through protein-ligand contact profiling, it was concluded that naringin formed more hydrogen bonds with TMPRSS2 and 3CLpro.</p><p dir="ltr">In contrast, hesperidin formed a more significant number of hydrogen bonds with PLpro. These observations were complimented by the 100 ns molecular dynamics simulation and binding free energy analysis, which showed a considerable stability of docked bioflavonoids in the active site of SARS-CoV-2 target proteins. Finally, the binding affinity and stability of the selected docked complexes were compared with the reference ligands (camostat for TMPRSS2, GC376 for 3CLpro, and GRL0617 for PLpro) that strongly inhibit their respective SARS-COV-2 targets. Overall analysis revealed that the selected flavonoids could be potential therapeutic agents against SARS-CoV-2. Naringin showed better affinity and stability for TMPRSS2 and 3CLpro, whereas hesperidin showed a better binding relationship and stability for PLpro.</p><h2>Other Information</h2><p dir="ltr">Published in: Computers in Biology and Medicine<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.compbiomed.2022.105231" target="_blank">https://dx.doi.org/10.1016/j.compbiomed.2022.105231</a></p>2022-03-01T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.compbiomed.2022.105231https://figshare.com/articles/journal_contribution/A_multi-targeted_approach_to_identify_potential_flavonoids_against_three_targets_in_the_SARS-CoV-2_life_cycle/24288028CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/242880282022-03-01T00:00:00Z |
| spellingShingle | A multi-targeted approach to identify potential flavonoids against three targets in the SARS-CoV-2 life cycle Sanjay Kumar (8853) Biomedical and clinical sciences Cardiovascular medicine and haematology Medical biochemistry and metabolomics Natural products COVID-19 Computational studies COVID-19 drug discovery Glycosylated flavonoids Hesperidin NaringinIn silico SARS-CoV-2 TMPRSS2 3CLpro PLpro |
| status_str | publishedVersion |
| title | A multi-targeted approach to identify potential flavonoids against three targets in the SARS-CoV-2 life cycle |
| title_full | A multi-targeted approach to identify potential flavonoids against three targets in the SARS-CoV-2 life cycle |
| title_fullStr | A multi-targeted approach to identify potential flavonoids against three targets in the SARS-CoV-2 life cycle |
| title_full_unstemmed | A multi-targeted approach to identify potential flavonoids against three targets in the SARS-CoV-2 life cycle |
| title_short | A multi-targeted approach to identify potential flavonoids against three targets in the SARS-CoV-2 life cycle |
| title_sort | A multi-targeted approach to identify potential flavonoids against three targets in the SARS-CoV-2 life cycle |
| topic | Biomedical and clinical sciences Cardiovascular medicine and haematology Medical biochemistry and metabolomics Natural products COVID-19 Computational studies COVID-19 drug discovery Glycosylated flavonoids Hesperidin NaringinIn silico SARS-CoV-2 TMPRSS2 3CLpro PLpro |