Computational and in vitro evaluation of sumac-derived ©Rutan compounds towards Sars-CoV-2 Mpro inhibition
The emergence of the SARS-CoV-2 virus caused the COVID-19 outbreak leading to a global pandemic. Natural substances started being screened for their antiviral activity by computational and in-vitro techniques. Here, we evaluated the anti-SARS-CoV-2 main protease (Mpro) efficacy of ©Rutan, which cont...
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Frontiers Media S.A.
2025-02-01
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| author | Muzaffar Kayumov Parthiban Marimuthu Parthiban Marimuthu Jamoliddin Razzokov Jamoliddin Razzokov Jamoliddin Razzokov Nurkhodja Mukhamedov Nurkhodja Mukhamedov Akmal Asrorov Nodir S. Berdiev Jamolitdin F. Ziyavitdinov Ansor Yashinov Ansor Yashinov Yuliya Oshchepkova Shavkat Salikhov Sharafitdin Mirzaakhmedov |
| author_facet | Muzaffar Kayumov Parthiban Marimuthu Parthiban Marimuthu Jamoliddin Razzokov Jamoliddin Razzokov Jamoliddin Razzokov Nurkhodja Mukhamedov Nurkhodja Mukhamedov Akmal Asrorov Nodir S. Berdiev Jamolitdin F. Ziyavitdinov Ansor Yashinov Ansor Yashinov Yuliya Oshchepkova Shavkat Salikhov Sharafitdin Mirzaakhmedov |
| author_sort | Muzaffar Kayumov |
| collection | DOAJ |
| description | The emergence of the SARS-CoV-2 virus caused the COVID-19 outbreak leading to a global pandemic. Natural substances started being screened for their antiviral activity by computational and in-vitro techniques. Here, we evaluated the anti-SARS-CoV-2 main protease (Mpro) efficacy of ©Rutan, which contains five polyphenols (R5, R6, R7, R7’, and R8) extracted from sumac Rhus coriaria L. We obtained three fractions after large-scale purification: fraction 1 held R5, fraction 2 consisted of R6, R7 and R7’, and fraction 3 held R8. In vitro results showed their anti-Mpro potential: IC50 values of R5 and R8 made 42.52 µM and 5.48 µM, respectively. Further, we studied Mpro-polyphenol interactions by in silico analysis to understand mechanistic extrapolation of Rutan binding nature with Mpro. We extensively incorporated a series of in silico techniques. Initially, for the docking protocol validation, redocking of the co-crystal ligand GC-376* to the binding pocket of Mpro was carried out. The representative docked complexes were subjected to long-range 500 ns molecular dynamics simulations. The binding free energy (BFE in kcal/mol) of components were calculated as follows: R8 (−104.636) > R6 (−93.754) > R7’ (−92.113) > R5 (−81.115) > R7 (−67.243). In silico results of R5 and R8 correspond with their in vitro outcomes. Furthermore, the per-residue decomposition analysis showed C145, E166, and Q189 residues as the hotspot residues for components contributing to maximum BFE energies. All five components effectively interact with the catalytic pocket of Mpro and form stable complexes that allow the estimation of their inhibitory activity. Assay kit analyses revealed that Rutan and its components have effective anti-SARS-CoV-2 Mpro inhibitory activity. |
| format | Article |
| id | doaj-art-367e12654f144ed8a461db4cea53f4bd |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-367e12654f144ed8a461db4cea53f4bd2025-02-04T06:31:51ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-02-011610.3389/fphar.2025.15184631518463Computational and in vitro evaluation of sumac-derived ©Rutan compounds towards Sars-CoV-2 Mpro inhibitionMuzaffar Kayumov0Parthiban Marimuthu1Parthiban Marimuthu2Jamoliddin Razzokov3Jamoliddin Razzokov4Jamoliddin Razzokov5Nurkhodja Mukhamedov6Nurkhodja Mukhamedov7Akmal Asrorov8Nodir S. Berdiev9Jamolitdin F. Ziyavitdinov10Ansor Yashinov11Ansor Yashinov12Yuliya Oshchepkova13Shavkat Salikhov14Sharafitdin Mirzaakhmedov15Institute of Bioorganic Chemistry, AS of Uzbekistan, Tashkent, UzbekistanPharmaceutical Science Laboratory (PSL-Pharmacy), Structural Bioinformatics Laboratory (SBL-Biochemistry), Faculty of Science and Engineering, Åbo Akademi University, Turku, FinlandCenter for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Chennai, IndiaInstitute of Fundamental and Applied Research, National Research University TIIAME, Tashkent, UzbekistanDepartment of Natural Sciences, Shakhrisabz State Pedagogical Institute, Shahrisabz, UzbekistanDepartment of Biotechnology, Tashkent State Technical University, Tashkent, UzbekistanInstitute of Bioorganic Chemistry, AS of Uzbekistan, Tashkent, UzbekistanDepartment of Natural Compounds and Applied Chemistry, National University of Uzbekistan, Tashkent, UzbekistanInstitute of Bioorganic Chemistry, AS of Uzbekistan, Tashkent, UzbekistanInstitute of Bioorganic Chemistry, AS of Uzbekistan, Tashkent, UzbekistanInstitute of Bioorganic Chemistry, AS of Uzbekistan, Tashkent, UzbekistanInstitute of Bioorganic Chemistry, AS of Uzbekistan, Tashkent, UzbekistanShanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, ChinaInstitute of Bioorganic Chemistry, AS of Uzbekistan, Tashkent, UzbekistanInstitute of Bioorganic Chemistry, AS of Uzbekistan, Tashkent, UzbekistanInstitute of Bioorganic Chemistry, AS of Uzbekistan, Tashkent, UzbekistanThe emergence of the SARS-CoV-2 virus caused the COVID-19 outbreak leading to a global pandemic. Natural substances started being screened for their antiviral activity by computational and in-vitro techniques. Here, we evaluated the anti-SARS-CoV-2 main protease (Mpro) efficacy of ©Rutan, which contains five polyphenols (R5, R6, R7, R7’, and R8) extracted from sumac Rhus coriaria L. We obtained three fractions after large-scale purification: fraction 1 held R5, fraction 2 consisted of R6, R7 and R7’, and fraction 3 held R8. In vitro results showed their anti-Mpro potential: IC50 values of R5 and R8 made 42.52 µM and 5.48 µM, respectively. Further, we studied Mpro-polyphenol interactions by in silico analysis to understand mechanistic extrapolation of Rutan binding nature with Mpro. We extensively incorporated a series of in silico techniques. Initially, for the docking protocol validation, redocking of the co-crystal ligand GC-376* to the binding pocket of Mpro was carried out. The representative docked complexes were subjected to long-range 500 ns molecular dynamics simulations. The binding free energy (BFE in kcal/mol) of components were calculated as follows: R8 (−104.636) > R6 (−93.754) > R7’ (−92.113) > R5 (−81.115) > R7 (−67.243). In silico results of R5 and R8 correspond with their in vitro outcomes. Furthermore, the per-residue decomposition analysis showed C145, E166, and Q189 residues as the hotspot residues for components contributing to maximum BFE energies. All five components effectively interact with the catalytic pocket of Mpro and form stable complexes that allow the estimation of their inhibitory activity. Assay kit analyses revealed that Rutan and its components have effective anti-SARS-CoV-2 Mpro inhibitory activity.https://www.frontiersin.org/articles/10.3389/fphar.2025.1518463/fullRutanSARS-CoV-2 MprodockingMD simulationsin vitro analysis |
| spellingShingle | Muzaffar Kayumov Parthiban Marimuthu Parthiban Marimuthu Jamoliddin Razzokov Jamoliddin Razzokov Jamoliddin Razzokov Nurkhodja Mukhamedov Nurkhodja Mukhamedov Akmal Asrorov Nodir S. Berdiev Jamolitdin F. Ziyavitdinov Ansor Yashinov Ansor Yashinov Yuliya Oshchepkova Shavkat Salikhov Sharafitdin Mirzaakhmedov Computational and in vitro evaluation of sumac-derived ©Rutan compounds towards Sars-CoV-2 Mpro inhibition Frontiers in Pharmacology Rutan SARS-CoV-2 Mpro docking MD simulations in vitro analysis |
| title | Computational and in vitro evaluation of sumac-derived ©Rutan compounds towards Sars-CoV-2 Mpro inhibition |
| title_full | Computational and in vitro evaluation of sumac-derived ©Rutan compounds towards Sars-CoV-2 Mpro inhibition |
| title_fullStr | Computational and in vitro evaluation of sumac-derived ©Rutan compounds towards Sars-CoV-2 Mpro inhibition |
| title_full_unstemmed | Computational and in vitro evaluation of sumac-derived ©Rutan compounds towards Sars-CoV-2 Mpro inhibition |
| title_short | Computational and in vitro evaluation of sumac-derived ©Rutan compounds towards Sars-CoV-2 Mpro inhibition |
| title_sort | computational and in vitro evaluation of sumac derived c rutan compounds towards sars cov 2 mpro inhibition |
| topic | Rutan SARS-CoV-2 Mpro docking MD simulations in vitro analysis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1518463/full |
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