Determination of Chemical Composition, Covid-19 Spike ACE2 Binding Inhibition Potential and In Silico Molecular Docking and Adme Properties of Gundelia Cappadocica Plant

Year 2025, Volume: 4 Issue: 2, 150 - 163, 31.07.2025

Fatih Çağlar Çelikezen , Aydın Baştin , Mehmet Fırat

https://doi.org/10.59312/ebshealth.1703441

Abstract

Aim: The present study was planned to investigate the anti-COVID-19 capacity of the ethanol extract of Gundelia cappadocica Fırat.
Method: For this purpose, the anti-COVID-19 effect was studied using commercial kits. In addition, plant content was determined by HPLC-DAD. ADME properties of the identified components were studied with SwissADME web tool, while molecular docking analysis was performed using CB-DOCK2 web tool.
Results: COVID-19 inhibition was found to be 9.61% at the highest concentration of 10 µl. Resveratrol, quercetin and chrysin fulfilled all drug-like molecule criteria. In molecular docking simulations, naringin molecule showed the highest binding affinity (∆G=-9.5 kcal/mol).
Conclusion:
These results suggest that Gundelia cappadocica can be used in the prevention and treatment of COVID19.

Keywords

Gundelia cappadocica , ACE 2 , Asteraceae , SwissADME , Molecular docking

Project Number

BEBAP 2023.21

GUNDELIA CAPPADOCICA BİTKİSİNİN KİMYASAL KOMPOZİSYONU, COVID-19 SPIKE ACE2 BAĞLANMA İNHİBİSYON POTANSİYELİ İLE IN SILICO MOLECULAR DOCKING VE ADME ÖZELLİKLERİNİN BELİRLENMESİ

Abstract

Amaç: Sunulan çalışma, Gundelia cappadocica Fırat’ın etanol ekstresinin anti-COVID-19 kapasitesini araştırmak amacıyla planlandı.
Yöntem: Bu amaçla, anti-COVID-19 etkisi ticari kitler kullanılarak çalışıldı. Bunun yanında, bitki içeriği HPLC-DAD ile tespit edildi. Belirlenen komponentlerin ADME özellikleri SwissADME web aracı ile çalışılırken, moleküler docking analizleri CB-DOCK2 web aracı kullanılarak yapıldı.
Bulgular: COVID-19 inhibisyonu en yüksek 10 µl konsantrasyonda %9.61 olarak bulundu. Resveratrol, kuersetin ve krisin ilaç benzeri molekül kriterlerinin tamamına uyum gösterdi. Moleküler docking simülasyonlarında ise en yüksek bağlanma afinitesini naringin molekülü gösterdi (∆G=-9.5 kcal/mol).
Sonuç: Bu sonuçlar, Gundelia cappadocica’nın COVID19’un önlenmesi ve tedavisinde kullanılabileceğini göstermektedir

Keywords

Gundelia cappadocica , ACE 2 , Asteraceae , SwissADME , Molecular docking

Ethical Statement

yok

Supporting Institution

Sunulan çalışma Bitlis Eren Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü tarafından 2023.21 nolu proje olarak desteklenmiştir.

Project Number

BEBAP 2023.21

References

• Acar, A. (2021). Evaluation of phenolic acids of Corylus avellana L. as potential SARS CoV-2 Main protease inhibitors. Erzincan University Journal of Science and Technology, 14(2), 492-509. doi: https://doi.org/10.18185/erzifbed.897348
• Ackerfield, J., Susanna, A., Funk, V., Kelch, D., Park, D. S., Thornhill, A. H., & Yildiz, B. (2020). A prickly puzzle: Generic delimitations in the Carduus‐Cirsium group (Compositae: Cardueae: Carduinae). Taxon, 69(4), 715-738. doi:https://doi.org/10.1002/tax.12288
• Adhikari, B., Marasini, B. P., Rayamajhee, B., Bhattarai, B. R., Lamichhane, G., Khadayat, K., & Parajuli, N. (2021). Potential roles of medicinal plants for the treatment of viral diseases focusing on COVID-19: A review. Phytotherapy Research, 35, 1298-1312. doi: https://doi.org/10.1002/ptr.6893.
• Aguiar, C., & Camps, I ( 2024). Molecular Docking in Drug Discovery: Techniques, Applications, and Advancements. Current Medicinal Chemistry.
• Akan, H., Korkut, M. M., & Balos, M. M. (2008). An ethnobotanical study around Arat Mountain and its surroundings (Birecik, Sanlıurfa). Fırat University Journal of Science and Engineering, 20, 67-81.
• Alam, S., Sarker, M. M. R., Afrin, S., Richi, F.T., Zhao, C., Zhou, J-R. & Mohamed, I. N. (2021). Traditional Herbal Medicines, Bioactive Metabolites, and Plant Products Against COVID-19: Update on Clinical Trials and Mechanism of Actions. Frontiers in pharmacology, 12, 671498. doi: 10.3389/fphar.2021.671498
• Beşler, Z. N., Bayraktar, D. Z., Koçak, M. C, & Kızıltan, G. (2024). Investigation of potential effects of quercetin on COVID-19 treatment: a systematic review of randomized controlled trials. Clinical Science of Nutrition, 6(2), 107-117. doi:10.62210/ClinSciNutr.2024.86,
• Bulut, C., & Kato, Y. (2020). Epidemiology of COVID-19. Turkish journal of medical sciences, 50(9), 563-570. doi:10.3906/sag-2004-172.
• Carlos, W. G., Cruz, C. S., Cao, B., & Pasnick, S. (2020). Novel Wuhan (2019-nCoV) Coronavirus. American Journal of Respiratory & Critical Care Medicine, 201(4), 7-8.
• Çayan, F., Deveci, E., Tel-Çayan, G.,&Duru, M.E. (2020). Identification and quantification of phenolic acid compounds of twenty-six mushrooms by HPLC–DAD. J Food Meas Charact 14(3):1690–1698.
• Çoruh, N., Celep, A. S., Özgökçe, F., & İşcan, M. (2007). Antioxidant capacities of Gundelia tournefortii L. extracts and inhibition on glutathione-S-transferase activity. Food Chemistry, 100(3), 1249-1253. doi:https://doi.org/10.1016/j.foodchem.2005.12.008
• Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: a free web tool to evaluate pharmacokinetics, druglikeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7(1), 42717. doi: 10.1038/srep42717 2017
• Dalar, A., Mukemre, M., Ünal, M., & Özgökce, F. (2018). Traditional medicinal plants of Ağrı province, Turkey. Journal of Ethnopharmacology, 226, 56-72. doi:https://doi.org/10.1016/j.jep.2018.08.004
• Dalar, A., Zengin, G., Mukemre, M., Bengu, A. S., & İşler, S. (2019). Gundelia rosea seed: Evaluation of biopharmaceutical potential and bioactive composition. South African Journal of Botany, 125, 505-510. doi:https://doi.org/10.1016/j.sajb.2019.08.024
• Egan, W.J., Merz, K.M. & Baldwin, J.J. (2000). Prediction of Drug Absorption Using Multivariate Statistics. Journal of Medicinal Chemistry, 43(21), 3867-3877.
• Elfiky, A.A. (2020). Natural products may interfere with SARS-CoV-2 attachment to the host cell. Journal of Biomolecular Structure and Dynamics, 39(9), 3194-3203.
• El Gizawy, H. A., Boshra, S. A., Mostafa, A., Mahmoud, S. H., Ismail, M. I., Alsfouk, A. A., ... & Al-Karmalawy, A. A. (2021). Pimenta dioica (L.) Merr. bioactive constituents exert anti-SARS-CoV-2 and anti-inflammatory activities: molecular docking and dynamics, in vitro, and in vivo studies. Molecules, 26(19), 5844.doi: 10.3390/molecules26195844.
• Emon, N. U., Alam, S., Rudra, S., Riya, S. R., Paul, A., Hossen, S. M. M., ... & Ganguly, A. (2021). Antidepressant, Anxiolytic, Antipyretic, and Thrombolytic Profiling of Methanol Extract of the Aerial Part of Piper Nigrum: In Vivo, In Vitro, and In Silico Approaches. Food Science & Nutrition, 9, 833–846. doi:10.1002/fsn3.2047
• Fırat, M. (2016). Four new species of Gundelia L. (Asteraceae) from Anatolia: G. komagenensis, G. colemerikensis, G. cilicica and G. anatolica. Vameda Ofset Press,Van, 32 pp.69.
• Fırat, M. (2017a). The resurrection and a new status of Gundelia tournefortii L.var. asperrima Trautv. (Asteraceae). OT Sistematik Botanik Dergisi, 24(2), 57-67.
• Fırat, M. (2017b). Gundelia mesopotamica (Asteraceae), a new lactiferous species from Mardin (Turkey). Acta Biologica Turcica, 30(3), 64-69.
• Fırat, M. (2017c). Gundelia rosea (Asteraceae), a new record for the Flora of Turkey with contributions to its systematics. Acta Biologica Turcica, 30(2), 31-35.
• Fırat, M. (2018a). A new status of Gundelia tournefortii L. forma purpurascens Bornm. (Asteraceae) and a new record for the flora of Turkey. OT Sistematik Botanik Dergisi, 25(1), 11-24.
• Fırat, M. (2018b). Gundelia armeniaca (Asteraceae), a species new to the flora of Turkey, with contributions to its taxonomy. Communications Faculty of Sciences University of Ankara Series C, 27(2), 35-46.
• Fırat, M. (2019a). New status of Gundelia tournefortii L. var. armata Freyn & Sint. (Asteraceae), and a new synonym of its. OT Sistematik Botanik Dergisi, 26 (1): 17-32.
• Fırat, M. (2019b). Gundelia siirtica (Asteraceae), a new lactiferous species from Siirt (south-eastern Anatolia). Phytotaxa, 394(4), 276-284.
• Fırat, M. (2021b). Gundelia cappadocica (Asteraceae); a new lactiferous species from Cappadocia (Kapadokya) Turkey, belonging to G. subg. Gundelia sect. Komagenenses Acta Biologica Turcica, 34(3), 128- 139.
• Geiger N, König EM, Oberwinkler H, Roll V, Diesendorf V, Fähr S, Obernolte H, Sewald K, Wronski S, Steinke M, & Bodem J. (2022). Acetylsalicylic Acid and Salicylic Acid Inhibit SARS-CoV-2 Replication in Precision-Cut Lung Slices. Vaccines, 10(10), 1619. doi: 10.3390/vaccines10101619.
• Halabi, S., Battah, A. A., Aburjai, T., & Hudaib, M. (2005). Phytochemical and Antiplatelet Investigation of Gundelia tournifortii. Pharmaceutical Biology, 43(6), 496-500. doi:https://doi.org/10.1080/13880200500220268
• Horne, J. R., & Vohl, M. C. (2020). Biological plausibility for interactions between dietary fat, resveratrol, ACE2, and SARS-CoV illness severity. American Journal of Physiology.Endocrinology and Metabolism, 318(5), 830–833. doi:https://doi.org/10.1152/ajpendo.00150.2020
• Jahan, I., & Onay, A. (2020). Potentials of Plant-Based Substance to Inhabit and Probable Cure for the COVID-19. Turkish Journal of Biology, 44(3), 228–241. doi:10.3906/biy-2005-114
• Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2012). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 64, 4-17. doi:https://doi.org/10.1016/j.addr.2012.09.019
• Liu, Y., Yang, X., Gan, J., Chen, S., Xiao, Z. X., & Cao, Y. (2022). CB-Dock2: Improved protein–ligand blind docking by integrating cavity detection, docking and homologous template fitting. Nucleic Acids Research, 50(W1), 159-164. doi:https://doi.org/10.1093/nar/gkac394
• Liu, S., Zhong, M., Wu, H., Su, W., Wang, Y.,& Li, P. (2024). Potential Beneficial Effects of Naringin and Naringenin on Long COVID-A Review of the Literature. Microorganisms, 12(2), 332. doi: 10.3390/microorganisms12020332
• Muegge, S.L. & Heald, D. (2001). Brittelli, Simple selection criteria for drug-like chemical matter. Journal of Medicinal Chemistry, 44(12), 1841-1846. doi: 0.1021/ jm015507e
• Ghose, A.K., Viswanadhan, V.N. & Wendoloski, J.J. (1999). A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases.Journal of Combinatorial Chemistry, 1(1), 55–68. doi: 10.1021/cc980007
• Perrella, F., Coppola, F., Petrone, A., Platella, C., Montesarchio, D., Stringaro, A., ... & Musumeci, D. (2021). Interference of polydatin/resveratrol in the ACE2: spike recognition during COVID-19 infection. A focus on their potential mechanism of action through computational and biochemical assays. Biomolecules, 11(7), 1048. doi: 10.3390/biom11071048
• Polat, B. (2012). Kayseri ve çevresinde yetişen bazı yabani meyvelerin biyoaktif özelliklerinin araştırılması. Kayseri: Yayımlanmamış Yüksek Lisans Tezi, Erciyes Üniversitesi Fen Bilimleri Enstitüsü.
• Rehman, M. T., AlAjmi, M. F., &Hussain, A. (2020). Natural Compounds as Inhibitors of SARS-CoV-2 Main Protease (3CLpro): A Molecular Docking and Simulation Approach to Combat COVID-19. Current Pharmaceutical Design, 27(33), 3577-3589. doi: 10.2174/1381612826999201116195851
• The Plant List, “Compositae”. (2021, 26 Haziran). http://www.theplantlist.org/browse/A/Compositae/ Qui, J. (2007). Traditional medicine: a culture in the balance. Nautre, 448(7150), 126-129.
• Saeed, A., Ahmad, B., Majaz, S., Nouroz, F., Ahmad, A., & Xie, Y. (2022). Targeting omicron and other reported SARS-CoV-2 lineages by potent inhibitors of main protease 3CL Mpro: molecular simulation analysis. Journal of Infection, 84(6), 133-136. doi: 10.1016/j.jinf.2022.02.012.
• Sarper, F., Akaydın, G., Yeşilada, E., & Şimşek, I. (2009). An ethnobotanical field survey in the Haymana district of Ankara province in Turkey. Turkish Journal of Biology, 33(1), 79-88. doi:10.3906/biy-0808-28
• Selvaraj, J., Rekha, U. V., Jh, S. F., Sivabalan, V., Ponnulakshmi, R., Vishnupriya, V., et al. (2021). Molecular docking analysis of SARS-CoV-2 linked RNA dependent RNA polymerase (RdRp) with compounds from Plectranthus amboinicus. Bioinformation, 17(1), 167-170.
• Shafiq, N., Mehroze, A., Sarwar, W., Arshad, U., Parveen, S., Rashid, M., Farooq, A., Rafiq, N., Wondmie, G. F., Bin Jardan, Y, A., Brogi, S.& Bourhia, M. (2023). Exploration of phenolic acid derivatives as inhibitors of SARS-CoV-2 main protease and receptor binding domain: potential candidates for anti-SARS-CoV-2 therapyFrontiers in Chemistry, 11, 1251529. doi: 10.3389/fchem.2023.1251529
• Srivastava, N., Garg, P., Srivastava, P.& Seth, P. K. (2021). A molecular dynamics simulation study of the ACE2 receptor with screened natural inhibitors to identify novel drug candidate against COVID-19. PeerJ, 9, e11171. Doi:https://doi.org/10.7717/peerj.11171
• Şekeroglu, N., Şenol, F. S., Orhan, I. E., Gülpınar, A. R., Kartal, M., & Şener, B. (2012). In vitro prospective effects of various traditional herbal coffees consumed in Anatolia linked to neurodegeneration. Food Research International, 45(1), 197-203. doi:https://doi.org/10.1016/j.foodres.2011.10.008
• Uce, İ., & Tunçtürk, M. (2014). Hakkâri’de doğal olarak yetişen ve yaygın olarak kullanılan bazı yabani bitkiler. Biyoloji Bilimleri Araştırma Dergisi, 7(2), 21-25.
• Veber, D.F., Johnson, S., Cheng, H.Y., Smith, B.R., Ward, K.W. & Kopple, K.D. (2002). Molecular Properties that İnfluence the Oral Bioavailability of Drug Candidates. Journal of Medicinal Chemistry, 45, 2615–2623.
• Wang, G., & Zhu, W. (2016). Molecular docking for drug discovery and development: a widely used approach but far from perfect. Future medicinal chemistry, 8(14), 1707–1710. https://doi.org/10.4155/fmc-2016-0143
• Yang, Y., Islam, M. S., Wang, J., Li, Y., & Chen, X. (2020). Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-new Coronavirus (SARS-CoV-2): a Review and Perspective. International Journal of Biological Sciences, 16(10), 1708. doi:10.7150/ijbs.45538
• Yang, X., Liu, Y., Gan, J., Xiao, Z. X., & Cao, Y. (2022). FitDock: protein–ligand docking by template fitting. Briefings In Bioinformatics, 23(3), bbac087. Doi: https://doi.org/10.1093/bib/bbac087
• Yıldız, B., & Aktoklu, E. (2010). Bitki sistematiği: ilkin karasal bitkilerden bir çeneklilere. Palme Yayıncılık.
• Yi, Y., Yu, R., Xue, H., Jin, Z., Zhang, M., Bao, Y.O., Wang, Z., Wei, H., Qiao, X., & Yang, H. (2024). Chrysin 7-O-β-D-glucuronide, a dual inhibitor of SARS-CoV-2 3CLpro and PLpro, for the prevention and treatment of COVID-19. International Journal of Antimicrobial Agents, 63(1):107039. doi: 10.1016/j.ijantimicag.2023.107039.