Favipiravir vs. Deferiprone: Tautomeric, photophysical, in vitro biological studies, and binding interactions with SARS-Cov-2-MPro/ACE2
Coronavirus disease 2019 (COVID-19) still remains the most disastrous infection continuously affecting millions of people worldwide. Herein, we performed a comparative study between the anti-influenza drug favipiravir (FAV) and the anti-thalassemia drug deferiprone (DFP) in order to examine their po...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Current Research in Biotechnology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590262824000029 |
| _version_ | 1827221832988622848 |
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| author | Nikolay T. Tzvetkov Martina I. Peeva Maya G. Georgieva Vera Deneva Aneliya A. Balacheva Ivan P. Bogdanov Maria Ponticelli Luigi Milella Kiril Kirilov Maima Matin Hans-Georg Stammler Atanas G. Atanasov Liudmil Antonov |
| author_facet | Nikolay T. Tzvetkov Martina I. Peeva Maya G. Georgieva Vera Deneva Aneliya A. Balacheva Ivan P. Bogdanov Maria Ponticelli Luigi Milella Kiril Kirilov Maima Matin Hans-Georg Stammler Atanas G. Atanasov Liudmil Antonov |
| author_sort | Nikolay T. Tzvetkov |
| collection | DOAJ |
| description | Coronavirus disease 2019 (COVID-19) still remains the most disastrous infection continuously affecting millions of people worldwide. Herein, we performed a comparative study between the anti-influenza drug favipiravir (FAV) and the anti-thalassemia drug deferiprone (DFP) in order to examine their potential as basic scaffolds for the generation of most effective and structurally novel antivirals. To conduct the initial molecular modelling and virtual screening steps, our recently proposed single crystal X-ray diffraction (SCXRD)/HYdrogen DEssolvation (HYDE) technology platform has been used. This platform allows molecular design, interactive prioritization and virtual evaluation of newly designed molecules, simultaneously affecting two COVID-related targets, including angiotensin-converting enzyme 2 (ACE2) as a host-cellular receptor (host-based approach) and the main protease (Mpro) enzyme of the spike glycoprotein of SARS-Cov-2 (virus-based approach). Based on the molecular docking results, DFP has shown higher binding affinity (Ki HYDE values) over FAV towards both biological targets. The tautomeric, physicochemical, and biological properties of FAV and DFP have been studied both experimentally and theoretically using molecular spectroscopy (UV–VIS absorption), parallel artificial membrane permeability assay, and cell biology (PAMPA and MTT assay), as well as DFT quantum chemical calculations. According to the obtained results, the enol tautomers of both compounds are considerably more stable in different organic solvents. However, the keto tautomer of FAV was estimated to be most preferable under physiological conditions, which is in good agreement with the molecular docking studies. The isolated crystal structure of DFP is in an excellent agreement with the computation in respect of the most stable tautomer. Combined single X-ray/molecular modeling studies including HYDE analyses provided not only insights into the protein–ligand interactions within the binding site of SARS-Cov-2-ACE2 and SARS-Cov-2-Mpro, but also a valuable information regarding the most stable enol tautomeric form of DFP that contributes to its estimated higher potency against these targets. |
| first_indexed | 2024-03-08T12:52:15Z |
| format | Article |
| id | doaj.art-43a24fed375146cd8f2208b687a21f4c |
| institution | Directory Open Access Journal |
| issn | 2590-2628 |
| language | English |
| last_indexed | 2025-03-21T16:28:52Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Biotechnology |
| spelling | doaj.art-43a24fed375146cd8f2208b687a21f4c2024-06-17T05:56:47ZengElsevierCurrent Research in Biotechnology2590-26282024-01-017100176Favipiravir vs. Deferiprone: Tautomeric, photophysical, in vitro biological studies, and binding interactions with SARS-Cov-2-MPro/ACE2Nikolay T. Tzvetkov0Martina I. Peeva1Maya G. Georgieva2Vera Deneva3Aneliya A. Balacheva4Ivan P. Bogdanov5Maria Ponticelli6Luigi Milella7Kiril Kirilov8Maima Matin9Hans-Georg Stammler10Atanas G. Atanasov11Liudmil Antonov12Department of Biochemical Pharmacology and Drug Design, Institute of Molecular Biology “Roumen Tsanev”, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 21, 1113 Sofia, Bulgaria; Corresponding author.Department of Biochemical Pharmacology and Drug Design, Institute of Molecular Biology “Roumen Tsanev”, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 21, 1113 Sofia, BulgariaDepartment of Biochemical Pharmacology and Drug Design, Institute of Molecular Biology “Roumen Tsanev”, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 21, 1113 Sofia, BulgariaInstitute of Electronics, Bulgarian Academy of Sciences, 1784 Sofia, Bulgaria; Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaDepartment of Biochemical Pharmacology and Drug Design, Institute of Molecular Biology “Roumen Tsanev”, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 21, 1113 Sofia, BulgariaDepartment of Biochemical Pharmacology and Drug Design, Institute of Molecular Biology “Roumen Tsanev”, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 21, 1113 Sofia, BulgariaDepartment of Science, University of Basilicata, V.le dell’Ateneo Lucano 10, 85100 Potenza, ItalyDepartment of Science, University of Basilicata, V.le dell’Ateneo Lucano 10, 85100 Potenza, Italy; Spinoff Bioactiplant, V.le dell’Ateneo Lucano 10, 85100 Potenza, ItalyDepartment of Biochemical Pharmacology and Drug Design, Institute of Molecular Biology “Roumen Tsanev”, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 21, 1113 Sofia, Bulgaria; Department of Natural Sciences, New Bulgarian University, 21 Montevideo Str., Sofia 1618, BulgariaInstitute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, Jastrzebiec, 05-552 Magdalenka, PolandDepartment of Chemistry, University of Bielefeld, Universitätsstr. 25, 33615 Bielefeld, GermanyInstitute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, Jastrzebiec, 05-552 Magdalenka, Poland; Ludwig Boltzmann Institute Digital Health and Patient Safety, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, AustriaInstitute of Electronics, Bulgarian Academy of Sciences, 1784 Sofia, BulgariaCoronavirus disease 2019 (COVID-19) still remains the most disastrous infection continuously affecting millions of people worldwide. Herein, we performed a comparative study between the anti-influenza drug favipiravir (FAV) and the anti-thalassemia drug deferiprone (DFP) in order to examine their potential as basic scaffolds for the generation of most effective and structurally novel antivirals. To conduct the initial molecular modelling and virtual screening steps, our recently proposed single crystal X-ray diffraction (SCXRD)/HYdrogen DEssolvation (HYDE) technology platform has been used. This platform allows molecular design, interactive prioritization and virtual evaluation of newly designed molecules, simultaneously affecting two COVID-related targets, including angiotensin-converting enzyme 2 (ACE2) as a host-cellular receptor (host-based approach) and the main protease (Mpro) enzyme of the spike glycoprotein of SARS-Cov-2 (virus-based approach). Based on the molecular docking results, DFP has shown higher binding affinity (Ki HYDE values) over FAV towards both biological targets. The tautomeric, physicochemical, and biological properties of FAV and DFP have been studied both experimentally and theoretically using molecular spectroscopy (UV–VIS absorption), parallel artificial membrane permeability assay, and cell biology (PAMPA and MTT assay), as well as DFT quantum chemical calculations. According to the obtained results, the enol tautomers of both compounds are considerably more stable in different organic solvents. However, the keto tautomer of FAV was estimated to be most preferable under physiological conditions, which is in good agreement with the molecular docking studies. The isolated crystal structure of DFP is in an excellent agreement with the computation in respect of the most stable tautomer. Combined single X-ray/molecular modeling studies including HYDE analyses provided not only insights into the protein–ligand interactions within the binding site of SARS-Cov-2-ACE2 and SARS-Cov-2-Mpro, but also a valuable information regarding the most stable enol tautomeric form of DFP that contributes to its estimated higher potency against these targets.http://www.sciencedirect.com/science/article/pii/S2590262824000029FavipiravirDeferiproneTautomer-based drug designCOVID-19Molecular modellingTautomerism |
| spellingShingle | Nikolay T. Tzvetkov Martina I. Peeva Maya G. Georgieva Vera Deneva Aneliya A. Balacheva Ivan P. Bogdanov Maria Ponticelli Luigi Milella Kiril Kirilov Maima Matin Hans-Georg Stammler Atanas G. Atanasov Liudmil Antonov Favipiravir vs. Deferiprone: Tautomeric, photophysical, in vitro biological studies, and binding interactions with SARS-Cov-2-MPro/ACE2 Current Research in Biotechnology Favipiravir Deferiprone Tautomer-based drug design COVID-19 Molecular modelling Tautomerism |
| title | Favipiravir vs. Deferiprone: Tautomeric, photophysical, in vitro biological studies, and binding interactions with SARS-Cov-2-MPro/ACE2 |
| title_full | Favipiravir vs. Deferiprone: Tautomeric, photophysical, in vitro biological studies, and binding interactions with SARS-Cov-2-MPro/ACE2 |
| title_fullStr | Favipiravir vs. Deferiprone: Tautomeric, photophysical, in vitro biological studies, and binding interactions with SARS-Cov-2-MPro/ACE2 |
| title_full_unstemmed | Favipiravir vs. Deferiprone: Tautomeric, photophysical, in vitro biological studies, and binding interactions with SARS-Cov-2-MPro/ACE2 |
| title_short | Favipiravir vs. Deferiprone: Tautomeric, photophysical, in vitro biological studies, and binding interactions with SARS-Cov-2-MPro/ACE2 |
| title_sort | favipiravir vs deferiprone tautomeric photophysical in vitro biological studies and binding interactions with sars cov 2 mpro ace2 |
| topic | Favipiravir Deferiprone Tautomer-based drug design COVID-19 Molecular modelling Tautomerism |
| url | http://www.sciencedirect.com/science/article/pii/S2590262824000029 |
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