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Current Computer-Aided Drug Design

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ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

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Research Article

Quinic and Digallic acids from Pistacia atlantica Desf. Leaves Extracts as Potent Dual Effect Inhibitors against main Protease and RNA-dependent RNA Polymerase of SARS-CoV-2

Author(s): Mebarka Imane Benguechoua*, Khedidja Benarous, Ziyad Benahmed, Sarah Boukhalkhal, Artur M. S. Silva and Mohamed Yousfi

Volume 18, Issue 4, 2022

Published on: 23 September, 2022

Page: [307 - 317] Pages: 11

DOI: 10.2174/1573409918666220616121449

Price: $65

Abstract

Background: Through this study, the Chemical composition realized by UHPLC-DADESI- MSn allowed the detection of different phenolic compound groups from Pistacia atlantica Desf. leaves extracts. We studied the inhibition of main protease (CL3 Mpro) and RNA-dependent RNA polymerase (RdRp) of the SARS-CoV-2 by the identified molecules through molecular docking.

Objective: The objective of this study is to identify compounds from Pistacia atlantica Desf. leaves extracts, which might have anti-viral effects.

Methods: Chemical composition was realized by UHPLC-DAD-ESI-MSn, and the inhibition of the main protease (CL3 Mpro) and RNA-dependent RNA polymerase (RdRp) of the SARS-CoV-2 was studied using molecular docking with Autodock Vina software. ADMET analysis was carried out.

Results: The identified compounds are quinic acid, digallic acid, galloylquinic acid, gallic acid, trigallic acid, digalloylquinic acids, trigalloylquinic acids and methyl gallate; digallic and quinic acids are the best inhibitors. Digallic acid had binding affinity energy (BAE) of -8.2 kcal/mol, and Ki of 1μM for the CL3 Mpro, Ki of 0.62 mM for the RdRp. Quinic acid showed Ki of 4.6 mM, recorded for both enzymes. Through ADMET analysis, we have found that the two molecules are good drug candidates.

Conclusion: This is the first time that a group of identified compounds from Pistacia atlantica Desf. leaves are studied for their potential activity against the novel virus by inhibiting two key enzymes in its life cycle, and no further studies have been published in this context.

Keywords: Quinic & digallic acids, main protease, RNA-dependent RNA polymerase, inhibitor, SARS-CoV-2, Pistacia atlantica desf. leaves.

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[1]
Al-Balas, M.; Al-Balas, H.I.; Al-Balas, H. Surgery during the COVID-19 pandemic: A comprehensive overview and perioperative care. Am. J. Surg., 2020, 219(6), 903-906. [https://www.ncbi. nlm.nih.gov/pmc/articles/PMC7166034/
[http://dx.doi.org/10.1016/j.amjsurg.2020.04.018] [PMID: 32334800]
[2]
Li, Q.; Guan, X.; Wu, P.; Wang, X.; Zhou, L.; Tong, Y.; Ren, R.; Leung, K.S.M.; Lau, E.H.Y.; Wong, J.Y.; Xing, X.; Xiang, N.; Wu, Y.; Li, C.; Chen, Q.; Li, D.; Liu, T.; Zhao, J.; Liu, M.; Tu, W.; Chen, C.; Jin, L.; Yang, R.; Wang, Q.; Zhou, S.; Wang, R.; Liu, H.; Luo, Y.; Liu, Y.; Shao, G.; Li, H.; Tao, Z.; Yang, Y.; Deng, Z.; Liu, B.; Ma, Z.; Zhang, Y.; Shi, G.; Lam, T.T.Y.; Wu, J.T.; Gao, G.F.; Cowling, B.J.; Yang, B.; Leung, G.M.; Feng, Z. Early transmission dynamics in Wuhan, China, of novel Coronavirus-infected pneumonia. N. Engl. J. Med., 2020, 382(13), 1199-1207.
[http://dx.doi.org/10.1056/NEJMoa2001316] [PMID: 31995857]
[3]
Guan, W-J.; Ni, Z-Y.; Hu, Y.; Liang, W-H.; Ou, C-Q.; He, J-X.; Liu, L.; Shan, H.; Lei, C.L.; Hui, D.S.C.; Du, B.; Li, L.J.; Zeng, G.; Yuen, K.Y.; Chen, R.C.; Tang, C.L.; Wang, T.; Chen, P.Y.; Xiang, J.; Li, S.Y.; Wang, J.L.; Liang, Z.J.; Peng, Y.X.; Wei, L.; Liu, Y.; Hu, Y.H.; Peng, P.; Wang, J.M.; Liu, J.Y.; Chen, Z.; Li, G.; Zheng, Z.J.; Qiu, S.Q.; Luo, J.; Ye, C.J.; Zhu, S.Y.; Zhong, N.S. Clinical characteristics of Coro-navirus disease 2019 in China. N. Engl. J. Med., 2020, 382(18), 1708-1720.
[http://dx.doi.org/10.1056/NEJMoa2002032] [PMID: 32109013]
[4]
Zheng, S-Q.; Yang, L.; Zhou, P-X.; Li, H-B.; Liu, F.; Zhao, R-S. Recommendations and guidance for providing pharmaceutical care services during COVID-19 pandemic: A china perspective. Res. Social Adm. Pharm., 2021, 17(1), 1819-1824.
[http://dx.doi.org/10.1016/j.sapharm.2020.03.012] [PMID: 32249102]
[5]
Dai, W.; Zhang, B.; Jiang, X-M.; Su, H.; Li, J.; Zhao, Y. Structure-based design, synthesis and biological evaluation of peptidomimetic alde-hydes as a novel series of antiviral drug candidates targeting the SARS-CoV-2 main protease. bioRxiv, 2020. Preprint.
[http://dx.doi.org/10.1101/2020.03.25.996348]
[6]
Sifi, I.; Gourine, N.; Gaydou, E.M.; Yousfi, M. Chemotypes of essential oil of unripe galls of Pistacia atlantica Desf. from Algeria. Nat. Prod. Res., 2015, 29(20), 1945-1949.
[http://dx.doi.org/10.1080/14786419.2015.1012164] [PMID: 25707439]
[7]
Ben Ahmed, Z.; Yousfi, M.; Viaene, J.; Dejaegher, B.; Demeyer, K.; Mangelings, D.; Vander Heyden, Y. Seasonal, gender and regional vari-ations in total phenolic, flavonoid, and condensed tannins contents and in antioxidant properties from Pistacia atlantica ssp. leaves. Pharm. Biol., 2017, 55(1), 1185-1194.
[http://dx.doi.org/10.1080/13880209.2017.1291690] [PMID: 28245729]
[8]
Ahmed, Z.B.; Yousfi, M.; Viaene, J.; Dejaegher, B.; Demeyer, K.; Mangelings, D.; Vander Heyden, Y. Potentially antidiabetic and antihyper-tensive compounds identified from Pistacia atlantica leaf extracts by LC fingerprinting. J. Pharm. Biomed. Anal., 2018, 149, 547-556.
[http://dx.doi.org/10.1016/j.jpba.2017.11.049] [PMID: 29190580]
[9]
Asma, A.; Boumediene, T.; Mohammed, B.; Nourelhouda, T.; Mebrouka, B.; Nourelhouda, T.; Mebrouka, B. Antibacterial activity and physicochemical characteristics of Pistacia atlantica extracts. 8, 162-168.
[10]
Hajjaj, G.; Bahlouli, A.; Sayah, K.; Tajani, M.; Cherrah, Y.; Zellou, A. Phytochemical screening and in vivo antipyretic activity of the aque-ous extracts of three Moroccan medicinal plants. Pharm Biol Evaluations [Internet], 2017, 4(4), 188.
[http://dx.doi.org/10.26510/2394-0859.pbe.2017.30]
[11]
Khodavaisy, S.; Rezaie, S.; Noorbakhsh, F.; Baghdadi, E.; Sharifynia, S.; Aala, F. Effects of Pistacia atlantica subsp. kurdica on growth and aflatoxin production by Aspergillus parasiticus. Jundishapur J. Microbiol., 2016, 9(7), e35452.
[http://dx.doi.org/10.5812/jjm.35452] [PMID: 27800127]
[12]
Jo, S.; Kim, S.; Shin, D.H.; Kim, M-S. Inhibition of SARS-CoV 3CL protease by flavonoids. J. Enzyme Inhib. Med. Chem., 2020, 35(1), 145-151.
[http://dx.doi.org/10.1080/14756366.2019.1690480] [PMID: 31724441]
[13]
Ben Ahmed, Z.; Yousfi, M.; Viaene, J.; Dejaegher, B.; Demeyer, K.; Mangelings, D.; Vander Heyden, Y. Antioxidant activities of Pistacia atlantica extracts modeled as a function of chromatographic fingerprints in order to identify antioxidant markers. Microchem. J., 2016, 128, 208-217. [Internet]
[http://dx.doi.org/10.1016/j.microc.2016.04.023]
[14]
Serseg, T.; Benarous, K.; Yousfi, M. Hispidin and Lepidine E: Two natural compounds and folic acid as potential inhibitors of 2019-novel coronavirus main protease (2019- nCoVMpro), molecular docking and SAR study. Curr. Computeraided Drug Des., 2021, 17(3), 469-479.
[http://dx.doi.org/10.2174/1573409916666200422075440] [PMID: 32321407]
[15]
Benarous, K.; Serseg, T.; Yousfi, M. Amoxicillin trihydrate-clavulanate potassium as potential inhibitor of 2019 novel Coronavirus main protease with strong receptor-binding domain (RBD), molecular docking and SAR study. SSRN Electron J, 2020. Internet
[http://dx.doi.org/10.2139/ssrn.3580230]
[16]
Linani, A.; Benarous, K.; Yousfi, M. Novel structural mechanism of Glutathione as a potential peptide inhibitor to the Main Protease (Mpro): CoviD-19 treatment, molecular docking and SAR study ChemRxiv, 2020. Preprint.
[http://dx.doi.org/10.26434/chemrxiv.12153021.v1]
[17]
Hertog, M.G.; Feskens, E.J.; Hollman, P.C.; Katan, M.B.; Kromhout, D. Dietary antioxidant flavonoids and risk of coronary heart disease: The zutphen elderly study. Lancet, 1993, 342(8878), 1007-1011.
[http://dx.doi.org/10.1016/0140-6736(93)92876-U] [PMID: 8105262]
[18]
Djeridane, A.; Yousfi, M.; Nadjemi, B.; Boutassouna, D.; Stocker, P.; Vidal, N. Antioxidant activity of some algerian medicinal plants ex-tracts containing phenolic compounds. Food Chem., 2006, 97(4), 654-660.
[http://dx.doi.org/10.1016/j.foodchem.2005.04.028]
[19]
Yin, W.; Mao, C.; Luan, X.; Shen, D-D.; Shen, Q.; Su, H.; Wang, X.; Zhou, F.; Zhao, W.; Gao, M.; Chang, S.; Xie, Y.C.; Tian, G.; Jiang, H.W.; Tao, S.C.; Shen, J.; Jiang, Y.; Jiang, H.; Xu, Y.; Zhang, S.; Zhang, Y.; Xu, H.E. Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science, 2020, 368(6498), 1499-1504.
[http://dx.doi.org/10.1126/science.abc1560] [PMID: 32358203]
[20]
Khallouki, F.; Breuer, A.; Merieme, E.; Ulrich, C.M.; Owen, R.W. Characterization and quantitation of the polyphenolic compounds detected in methanol extracts of Pistacia atlantica Desf. Fruits from the Guelmim region of Morocco. J. Pharm. Biomed. Anal., 2017, 134, 310-318.
[http://dx.doi.org/10.1016/j.jpba.2016.11.023] [PMID: 27984819]
[21]
Santos, S.A.O.; Vilela, C.; Freire, C.S.R.; Neto, C.P.; Silvestre, A.J.D. Ultra-high performance liquid chromatography coupled to mass spec-trometry applied to the identification of valuable phenolic compounds from Eucalyptus wood. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2013, 938, 65-74.
[http://dx.doi.org/10.1016/j.jchromb.2013.08.034] [PMID: 24055752]
[22]
Wyrepkowski, C.C.; Costa, D.L.; Sinhorin, A.P.; Vilegas, W.; De Grandis, R.A.; Resende, F.A.; Varanda, E.A.; dos Santos, L.C. Characteri-zation and quantification of the compounds of the ethanolic extract from Caesalpinia ferrea stem bark and evaluation of their mutagenic ac-tivity. Molecules, 2014, 19(10), 16039-16057.
[http://dx.doi.org/10.3390/molecules191016039] [PMID: 25299821]
[23]
Abu-Reidah, I.M.; Ali-Shtayeh, M.S.; Jamous, R.M.; Arráez-Román, D.; Segura-Carretero, A. HPLC-DAD-ESI-MS/MS screening of bioac-tive components from Rhus coriaria L. (Sumac) fruits. Food Chem., 2015, 166, 179-191.
[http://dx.doi.org/10.1016/j.foodchem.2014.06.011] [PMID: 25053044]
[24]
Erşan, S.; Güçlü Üstündağ, Ö.; Carle, R.; Schweiggert, R.M. Identification of phenolic compounds in red and green pistachio (Pistacia vera L.) Hulls (Exo- and Mesocarp) by HPLC-DAD-ESI-(HR)-MS(n). J. Agric. Food Chem., 2016, 64(26), 5334-5344.
[http://dx.doi.org/10.1021/acs.jafc.6b01745] [PMID: 27292533]
[25]
Grace, M.H.; Esposito, D.; Timmers, M.A.; Xiong, J.; Yousef, G.; Komarnytsky, S.; Lila, M.A. Chemical composition, antioxidant and anti-inflammatory properties of pistachio hull extracts. Food Chem., 2016, 210, 85-95.
[http://dx.doi.org/10.1016/j.foodchem.2016.04.088] [PMID: 27211624]
[26]
Clifford, M.N.; Stoupi, S.; Kuhnert, N. Profiling and characterization by LC-MSn of the galloylquinic acids of green tea, tara tannin, and tannic acid. J. Agric. Food Chem., 2007, 55(8), 2797-2807.
[http://dx.doi.org/10.1021/jf063533l] [PMID: 17381119]
[27]
Barros, L.; Dueñas, M.; Ferreira, I.C.F.R.; Maria Carvalho, A.; Santos-Buelga, C. Use of HPLC–DAD–ESI/MS to profile phenolic com-pounds in edible wild greens from Portugal. Food Chem., 2011, 127(1), 169-173.
[http://dx.doi.org/10.1016/j.foodchem.2011.01.009]
[28]
Benamar, H.; Marouf, A.; Bennaceur, M. Phytochemical composition, antioxidant and acetylcholinesterase inhibitory activities of aqueous extract and fractions of Pistacia atlantica subsp. Atlantica from Algeria. J. Herbs Spices Med. Plants, 2018, 24(3), 229-244. [Internet]
[http://dx.doi.org/10.1080/10496475.2018.1446204]
[29]
Bampouli, A.; Kyriakopoulou, K.; Papaefstathiou, G.; Louli, V.; Krokida, M.; Magoulas, K. Comparison of different extraction methods of Pistacia lentiscus var. Chia leaves: Yield, antioxidant activity and essential oil chemical composition. J. Appl. Res. Med. Aromat. Plants, 2014, 1(3), 81-91.
[http://dx.doi.org/10.1016/j.jarmap.2014.07.001]
[30]
Han, J.; Ye, M.; Qiao, X.; Xu, M.; Wang, B-R.; Guo, D-A. Characterization of phenolic compounds in the Chinese herbal drug Artemisia annua by liquid chromatography coupled to electrospray ionization mass spectrometry. J. Pharm. Biomed. Anal., 2008, 47(3), 516-525.
[http://dx.doi.org/10.1016/j.jpba.2008.02.013] [PMID: 18394841]
[31]
March, R.E.; Miao, X-S.; Metcalfe, C.D. A fragmentation study of a flavone triglycoside, kaempferol-3-O-robinoside-7-O-rhamnoside. Rapid Commun. Mass Spectrom., 2004, 18(9), 931-934.
[http://dx.doi.org/10.1002/rcm.1428] [PMID: 15116418]
[32]
Schütz, K.; Kammerer, D.R.; Carle, R.; Schieber, A. Characterization of phenolic acids and flavonoids in dandelion (Taraxacum officinale WEB. Ex WIGG.) root and herb by high-performance liquid chromatography/electrospray ionization mass spectrometry: Phenolic acids and flavonoids in dandelion root and herb. Rapid Commun. Mass Spectrom., 2005, 19(2), 179-186.
[http://dx.doi.org/10.1002/rcm.1767] [PMID: 15593267]
[33]
Löffler, C.; Sahm, A.; Wray, V.; Czygan, F-C.; Proksch, P. Soluble phenolic constituents from cuscuta reflexa and cuscuta platyloba. Biochem. Syst. Ecol., 1995, 23(2), 121-128. [Internet]
[http://dx.doi.org/10.1016/0305-1978(95)93846-U]
[34]
El Bishbishy, M.H.; Gad, H.A.; Aborehab, N.M. Chemometric discrimination of three Pistacia species via their metabolic profiling and their possible in vitro effects on memory functions. J. Pharm. Biomed. Anal., 2020, 177(112840), 112840.
[http://dx.doi.org/10.1016/j.jpba.2019.112840] [PMID: 31522096]
[35]
Boukhalkhal, S.; Gourine, N.; Pinto, D.C.G.A.; Silva, A.M.S.; Yousfi, M. UHPLC-DAD-ESI-MSn profiling variability of the phenolic con-stituents of Artemisia campestris L. Populations growing in Algeria. Biocatal. Agric. Biotechnol., 2020, 23(101483), 101483. [Internet]
[http://dx.doi.org/10.1016/j.bcab.2019.101483]
[36]
Bhouri, W.; Derbel, S.; Skandrani, I.; Boubaker, J.; Bouhlel, I.; Sghaier, M.B.; Kilani, S.; Mariotte, A.M.; Dijoux-Franca, M.G.; Ghedira, K.; Chekir-Ghedira, L. Study of genotoxic, antigenotoxic and antioxidant activities of the digallic acid isolated from Pistacia lentiscus fruits. Toxicol. In Vitro, 2010, 24(2), 509-515.
[http://dx.doi.org/10.1016/j.tiv.2009.06.024] [PMID: 19563883]
[37]
Bozorgi, M.; Memariani, Z.; Mobli, M.; Salehi Surmaghi, M.H.; Shams-Ardekani, M.R.; Rahimi, R. Five Pistacia species (P. vera, P. atlanti-ca, P. terebinthus, P. khinjuk, and P. lentiscus): A review of their traditional uses, phytochemistry, and pharmacology. Scientific World J., 2013, 2013, 219815.
[http://dx.doi.org/10.1155/2013/219815] [PMID: 24453812]
[38]
Kaihatsu, K. Potential anti-influenza virus agents based on coffee ingredients and natural flavonols. Nat. Prod. Chem. Res., 2014, 2(2) [In-ternet]
[http://dx.doi.org/10.4172/2329-6836.1000129]
[39]
Papetti, A.; Mascherpa, D.; Carazzone, C.; Stauder, M.; Spratt, D.A.; Wilson, M.; Pratten, J.; Ciric, L.; Lingström, P.; Zaura, E.; Weiss, E.; Ofek, I.; Signoretto, C.; Pruzzo, C.; Gazzani, G. Identification of organic acids in Cichorium intybus inhibiting virulence-related properties of oral pathogenic bacteria. Food Chem., 2013, 138(2-3), 1706-1712.
[http://dx.doi.org/10.1016/j.foodchem.2012.10.148] [PMID: 23411301]

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