دورية أكاديمية
In Silico Analysis of the Antidepressant Fluoxetine and Related Drugs at SARS-CoV-2 Main Protease (M pro ) and Papain-like Protease (PL pro ).
| العنوان: | In Silico Analysis of the Antidepressant Fluoxetine and Related Drugs at SARS-CoV-2 Main Protease (M pro ) and Papain-like Protease (PL pro ). |
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| المؤلفون: | Tronco Pauletto PJ; Department of Biochemistry and Molecular Biology, Federal University of Santa Maria (UFSM), 97105-900, RS, Brazil., Omage FB; Department of Biochemistry and Molecular Biology, Federal University of Santa Maria (UFSM), 97105-900, RS, Brazil., Delgado CP; Department of Biochemistry and Molecular Biology, Federal University of Santa Maria (UFSM), 97105-900, RS, Brazil., Nogara PA; Department of Biochemistry and Molecular Biology, Federal University of Santa Maria (UFSM), 97105-900, RS, Brazil., Teixeira Rocha JB; Department of Biochemistry and Molecular Biology, Federal University of Santa Maria (UFSM), 97105-900, RS, Brazil. |
| المصدر: | Current drug discovery technologies [Curr Drug Discov Technol] 2023; Vol. 20 (2), pp. e101022209771. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Bentham Science Publishers Country of Publication: United Arab Emirates NLM ID: 101157212 Publication Model: Print Cited Medium: Internet ISSN: 1875-6220 (Electronic) Linking ISSN: 15701638 NLM ISO Abbreviation: Curr Drug Discov Technol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Sharjah, U.A.E. ; San Francisco, CA : Bentham Science Publishers, c2004- |
| مواضيع طبية MeSH: | COVID-19*, Humans ; SARS-CoV-2 ; Molecular Docking Simulation ; Papain ; Fluoxetine/pharmacology ; Fluoxetine/therapeutic use ; Selective Serotonin Reuptake Inhibitors/pharmacology ; Selective Serotonin Reuptake Inhibitors/therapeutic use ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Antiviral Agents/chemistry ; Peptide Hydrolases ; Citalopram ; Venlafaxine Hydrochloride/pharmacology ; Venlafaxine Hydrochloride/therapeutic use ; Protease Inhibitors/pharmacology ; Protease Inhibitors/therapeutic use ; Protease Inhibitors/chemistry ; Antidepressive Agents/pharmacology ; Antidepressive Agents/therapeutic use |
| مستخلص: | Background: SARS-CoV-2 main protease (M pro or 3CL pro ) and papain-like protease (PL pro ) are common viral targets for repurposed drugs to combat COVID-19 disease. Recently, several antidepressants (such as fluoxetine, venlafaxine and citalopram) belonging to the Selective Serotonin Reuptake Inhibitors (SSRIs) and the Serotonin-Norepinephrine Reuptake Inhibitors (SNRI) classes have been shown to in vitro inhibit viral replication. Aim: Investigate a possible action of fluoxetine and derivatives on SARS-CoV-2 protease sites. Methods: Molecular docking was performed using AutoDock Vina. Both protease structures and different drug conformations were used to explore the possibility of SARS-CoV-2 inhibition on a M pro or PL pro related pathway. Drug structures were obtained by optimization with the Avogadro software and MOPAC using the PM6 method. Results were analysed on Discovery Studio Visualizer. Results: The results indicated that M pro interacted in a thermodynamically favorable way with fluoxetine, venlafaxine, citalopram, atomoxetine, nisoxetine and norfluoxetine in the region of the active site, whether PL pro conformers did not come close to the active site. Conclusion: In an in silico perspective, it is likely that the SSRIs and other anti-depressants could interact with M pro and cause the enzyme to malfunction. Unfortunately, the same drugs did not present similar results on PLpro crystal, therefore, no inhibition is expected in an in vitro trial. Anyway, in vitro tests are necessary for a better understanding of the links between SARS-CoV-2 proteases and antidepressants. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.) |
| فهرسة مساهمة: | Keywords: Docking; M pro; PL pro; SARS-CoV-2; antidepressants; drug repurposing; proteases |
| المشرفين على المادة: | EC 3.4.22.2 (Papain) EC 3.4.22.- (3C-like proteinase, SARS-CoV-2) 01K63SUP8D (Fluoxetine) 0 (Selective Serotonin Reuptake Inhibitors) 0 (Antiviral Agents) EC 3.4.- (Peptide Hydrolases) 0DHU5B8D6V (Citalopram) 7D7RX5A8MO (Venlafaxine Hydrochloride) 0 (Protease Inhibitors) 0 (Antidepressive Agents) |
| تواريخ الأحداث: | Date Created: 20221012 Date Completed: 20230310 Latest Revision: 20230715 |
| رمز التحديث: | 20230715 |
| DOI: | 10.2174/1570163819666221010115118 |
| PMID: | 36221883 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1875-6220 |
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| DOI: | 10.2174/1570163819666221010115118 |