In silico Evaluation of ACE2 Inhibition by Prunus armeniaca L. and in vivo
Toxicity Study

Ismail      Bouadid; Soumia      Moujane; Mourad      Akdad; Moualij      Benaissa; Mohamed      Eddouks

doi:10.2174/011871529X265182231211103724

Abstract

Background: SARS-CoV-2 is a virus that uses ACE2 to enter the host cell.

Aims and Objectives: This study aimed to evaluate the in silico inhibitory activity of polyphenols from Prunus armeniaca (P. armeniaca) on angiotensin-converting enzyme 2 (ACE2).

Methods: The efficacy of phytocompounds from P. armeniaca in inhibiting ACE2 was tested through molecular docking and dynamic analyses. The toxicological analysis of P. armeniaca was also evaluated.

Results: A total of twenty polyphenols were docked against the ACE2 active site, and four compounds showed interesting profiles. In vivo acute toxicity study demonstrated that the aqueous extract of Prunus armeniaca was safe.

Conclusion: Four compounds from Prunus armeniaca seem to exert an inhibitory potential of ACE2.

Keywords: SARS-CoV-2, ACE2, Prunus armeniaca L., molecular docking, molecular dynamic simulation, toxicity.

« Previous Next »

Graphical Abstract

[1]
Salian, V.S.; Wright, J.A.; Vedell, P.T.; Nair, S.; Li, C.; Kandimalla, M.; Tang, X.; Carmona Porquera, E.M.; Kalari, K.R.; Kandimalla, K.K. COVID-19 transmission, current treatment, and future therapeutic strategies. Mol. Pharm.,  2021, 18(3), 754-771.
 [http://dx.doi.org/10.1021/acs.molpharmaceut.0c00608] [PMID:  33464914]

[2]
Ochani, R.; Asad, A.; Yasmin, F.; Shaikh, S.; Khalid, H.; Batra, S.; Sohail, M.R.; Mahmood, S.F.; Ochani, R.; Hussham Arshad, M.; Kumar, A.; Surani, S. COVID-19 pandemic: From origins to outcomes. A comprehensive review of viral pathogenesis, clinical manifestations, diagnostic evaluation, and management. Infez. Med.,  2021, 29(1), 20-36.
 [PMID:  33664170]

[3]
Khan, M.; Adil, S.F.; Alkhathlan, H.Z.; Tahir, M.N.; Saif, S.; Khan, M.; Khan, S.T. COVID-19: A global challenge with old history, epidemiology and progress so far. Molecules,  2020, 26(1), 39.
 [http://dx.doi.org/10.3390/molecules26010039] [PMID:  33374759]

[4]
Tang, D.; Comish, P.; Kang, R. The hallmarks of COVID-19 disease. PLoS Pathog.,  2020, 16(5), e1008536.
 [http://dx.doi.org/10.1371/journal.ppat.1008536] [PMID:  32442210]

[5]
Saxena, S.K.; Kumar, S.; Baxi, P.; Srivastava, N.; Puri, B.; Ratho, R.K. Chasing COVID-19 through SARS-CoV-2 spike glycoprotein. Virusdisease,  2020, 31(4), 399-407.
 [http://dx.doi.org/10.1007/s13337-020-00642-7] [PMID:  33313362]

[6]
Lu, R.; Zhao, X.; Li, J.; Niu, P.; Yang, B.; Wu, H.; Wang, W.; Song, H.; Huang, B.; Zhu, N.; Bi, Y.; Ma, X.; Zhan, F.; Wang, L.; Hu, T.; Zhou, H.; Hu, Z.; Zhou, W.; Zhao, L.; Chen, J.; Meng, Y.; Wang, J.; Lin, Y.; Yuan, J.; Xie, Z.; Ma, J.; Liu, W.J.; Wang, D.; Xu, W.; Holmes, E.C.; Gao, G.F.; Wu, G.; Chen, W.; Shi, W.; Tan, W. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet,  2020, 395(10224), 565-574.
 [http://dx.doi.org/10.1016/S0140-6736(20)30251-8] [PMID:  32007145]

[7]
Zhou, P.; Yang, X.L.; Wang, X.G.; Hu, B.; Zhang, L.; Zhang, W.; Si, H.R.; Zhu, Y.; Li, B.; Huang, C.L.; Chen, H.D.; Chen, J.; Luo, Y.; Guo, H.; Jiang, R.D.; Liu, M.Q.; Chen, Y.; Shen, X.R.; Wang, X.; Zheng, X.S.; Zhao, K.; Chen, Q.J.; Deng, F.; Liu, L.L.; Yan, B.; Zhan, F.X.; Wang, Y.Y.; Xiao, G.F.; Shi, Z.L. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature,  2020, 579(7798), 270-273.
 [http://dx.doi.org/10.1038/s41586-020-2012-7] [PMID:  32015507]

[8]
Cui, J.; Li, F.; Shi, Z.L. Origin and evolution of pathogenic coronaviruses. Nat. Rev. Microbiol.,  2019, 17(3), 181-192.
 [http://dx.doi.org/10.1038/s41579-018-0118-9] [PMID:  30531947]

[9]
Silakari, O.; Kumar Singh, P. Molecular Docking Analysis: Basic Technique to Predict Drug-Receptor Interactions.Concepts and Experimental Protocols of Modelling and Informatics in Drug Design; Academic Press: Cambridge, MA, USA, 2021, pp. 131-155.
 [http://dx.doi.org/10.1016/B978-0-12-820546-4.00006-4]

[10]
Anand, U.; Jacobo-Herrera, N.; Altemimi, A.; Lakhssassi, N. A comprehensive review on medicinal plants as antimicrobial therapeutics: Potential avenues of biocompatible drug discovery. Metabolites,  2019, 9(11), 258.
 [http://dx.doi.org/10.3390/metabo9110258] [PMID:  31683833]

[11]
Ben-Shabat, S.; Yarmolinsky, L.; Porat, D.; Dahan, A. Antiviral effect of phytochemicals from medicinal plants: Applications and drug delivery strategies. Drug Deliv. Transl. Res.,  2020, 10(2), 354-367.
 [http://dx.doi.org/10.1007/s13346-019-00691-6] [PMID:  31788762]

[12]
Eddouks, M.; Bouadid, I.; Akdad, M. Antihypertensive activity of prunus armeniaca in hypertensive rats. Cardiovasc. Hematol. Agents Med. Chem.,  2023, 21(1), 20-30.
 [http://dx.doi.org/10.2174/1871525720666220613164559] [PMID:  35702770]

[13]
Akdad, M.; Moujane, S.; Bouadid, I.; Benlyas, M.; Eddouks, M. Phytocompounds from Anvillea radiata as promising anti-Covid-19 drugs: in silico studies and in vivo safety assessment. J. Environ. Sci. Health Part A Tox. Hazard. Subst. Environ. Eng.,  2021, 56(14), 1512-1523.
 [http://dx.doi.org/10.1080/10934529.2021.2020029] [PMID:  34978275]

[14]
Moujane, S.; Bouadid, I.; Bouachrine, M.; Benlyas, M.; Filali-Zegzouti, Y.; Eddouks, M.; Moualij, B. Polyphenols from Prunus armeniaca L. as Promising Anticancer (Cervical Cancer): In silico studies and in vivo safety assessment. Advancements in Journal of Urology and Nephrology,  2022, 4, 50-59.

[15]
Nishad, D.K.; Mittal, G.; Chaurasia, O.P.; Kumar, R.; Bhatnagar, A.; Singh, S.B.; Ali, R.; Ali, R.; Jaimini, A. Acute and sub acute toxicity and efficacy studies of Hippophae rhamnoides based herbal antioxidant supplement. Indian J. Pharmacol.,  2012, 44(4), 504-508.
 [http://dx.doi.org/10.4103/0253-7613.99329] [PMID:  23087514]

[16]
PubChem.   Available from: https://pubchem.ncbi.nlm.nih.gov/
          (Accessed on: July 2, 2020).
        

[17]
 RCSB Protein Data Bank (RCSB PDB).   Available from: https://www.rcsb.org/
            (Accessed on: April 2, 2020).
         

[18]
BIOVIA Discovery Studio-System Requirements for Discovery Studio. 2020.  Available from: https://www.3dsbiovia.com/products/collaborative-science/biovi a-discovery-studio/requirements/technical-requirements-2020.html
          (Accessed on: April 2, 2020).
        

[19]
iGEMDOCK   Available from: http://gemdock.life.nctu.edu.tw/dock/igemdock.php
        	 Accessed on May 2, 2020).
        	

[20]
Yang, H.; Lou, C.; Sun, L.; Li, J.; Cai, Y.; Wang, Z.; Li, W.; Liu, G.; Tang, Y. admetSAR 2.0: web-service for prediction and optimization of chemical ADMET properties. Bioinformatics,  2019, 35(6), 1067-1069.
 [http://dx.doi.org/10.1093/bioinformatics/bty707] [PMID:  30165565]

[21]
Pires, D.E.V.; Blundell, T.L.; Ascher, D.B. pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. J. Med. Chem.,  2015, 58(9), 4066-4072.
 [http://dx.doi.org/10.1021/acs.jmedchem.5b00104] [PMID:  25860834]

[22]
Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem.,  2010, 31(2), 455-461.
 [http://dx.doi.org/10.1002/jcc.21334] [PMID:  19499576]

[23]
Téléchargements - MGLTools. 2020. Available from: http://mgltools.scripps.edu/downloads
          (Accessed on: April, 29,2020).
        

[24]
PyMOL 2020. Available from:  https://pymol.org/2/
            (Accessed	on: May, 12, 2020).
         

[25]
Bowers, K.J. Molecular dynamics-Scalable algorithms for molecular dynamics simulations on commodity clusters. In Proceedings of the 2006 ACM/IEEE conference on Supercomputing-SC ’06,  Tampa, Florida2006, p. 84.
 [http://dx.doi.org/10.1145/1188455.1188544]

[26]
Shivakumar, D.; Williams, J.; Wu, Y.; Damm, W.; Shelley, J.; Sherman, W. Prediction of absolute solvation free energies using molecular dynamics free energy perturbation and the OPLS force field. J. Chem. Theory Comput.,  2010, 6(5), 1509-1519.
 [http://dx.doi.org/10.1021/ct900587b] [PMID:  26615687]

[27]
Nakhleh, A.; Shehadeh, N. Interactions between antihyperglycemic drugs and the renin-angiotensin system: Putative roles in COVID-19. A mini-review. Diabetes Metab. Syndr.,  2020, 14(4), 509-512.
 [http://dx.doi.org/10.1016/j.dsx.2020.04.040] [PMID:  32388330]

[28]
Di Lorenzo, G.; Di Trolio, R.; Kozlakidis, Z.; Busto, G.; Ingenito, C.; Buonerba, L.; Ferrara, C.; Libroia, A.; Ragone, G.; Ioio, C.; Savastano, B.; Polverino, M.; De Falco, F.; Iaccarino, S.; Leo, E. COVID 19 therapies and anti-cancer drugs: A systematic review of recent literature. Crit. Rev. Oncol. Hematol.,  2020, 152, 102991.
 [http://dx.doi.org/10.1016/j.critrevonc.2020.102991] [PMID:  32544802]

[29]
Mohamad Zobir, S.Z.; Mohd Fauzi, F.; Liggi, S.; Drakakis, G.; Fu, X.; Fan, T.P.; Bender, A. Global mapping of traditional chinese medicine into bioactivity space and pathways annotation improves mechanistic understanding and discovers relationships between therapeutic action (Sub)classes. Evid. Based Complement. Alternat. Med.,  2016, 2016, 1-25.
 [http://dx.doi.org/10.1155/2016/2106465] [PMID:  26989424]

[30]
Erdogan-Orhan, I.; Kartal, M. Insights into research on phytochemistry and biological activities of Prunus armeniaca L. (apricot). Food Res. Int.,  2011, 44(5), 1238-1243.
 [http://dx.doi.org/10.1016/j.foodres.2010.11.014]

[31]
Raj, V.; Mishra, A.K.; Mishra, A.; Khan, N.A. Hepatoprotective effect of Prunus armeniaca L. (Apricot) leaf extracts on Paracetamol induced liver damage in Wistar rats. Pharmacogn. J.,  2016, 8(2), 154-158.
 [http://dx.doi.org/10.5530/pj.2016.2.9]

[32]
Dasgupta, K.; Thilmony, R.; Stover, E.; Oliveira, M.L.; Thomson, J. Novel R2R3-MYB transcription factors from Prunus americana regulate differential patterns of anthocyanin accumulation in tobacco and citrus. GM Crops Food,  2017, 8(2), 85-105.
 [http://dx.doi.org/10.1080/21645698.2016.1267897] [PMID:  28051907]

[33]
S, P. Toxicological screening. J. Pharmacol. Pharmacother.,  2011, 2(2), 74-79.
 [http://dx.doi.org/10.4103/0976-500X.81895] [PMID:  21772764]

[34]
Ogobuiro, I.; Tuma, F. Physiology, renal. In: In: StatPearls; Treasure Island, (FL), 2022. 

[35]
Meharie, B.G.; Tunta, T.A. Evaluation of diuretic activity and phytochemical contents of aqueous extract of the shoot apex of Podocarpus falcactus. J. Exp. Pharmacol.,  2020, 12, 629-641.
 [http://dx.doi.org/10.2147/JEP.S287277] [PMID:  33364857]

[36]
M, R.; Oa, A-S.; Tm, E-H.; Aa, A-M. Effect of prolonged vigabatrin treatment on hematological and biochemical parameters in plasma, liver and kidney of Swiss albino mice. Sci. Pharm.,  2002, 70(2), 135-145.
 [http://dx.doi.org/10.3797/scipharm.aut-02-16]

[37]
Flores-Félix, J.D.; Gonçalves, A.C.; Alves, G.; Silva, L.R. Consumption of phenolic-rich food and dietary supplements as a key tool in SARS-CoV-19 infection. Foods,  2021, 10(9), 2084.
 [http://dx.doi.org/10.3390/foods10092084] [PMID:  34574194]

Rights & Permissions Print Cite

Article Metrics

20

4

Journal Information

For Authors

For Editors

For Reviewers

Explore Articles

Open Access

Open Access Articles

For Visitors

DOI https://dx.doi.org/10.2174/011871529X265182231211103724	Print ISSN 1871-529X
Publisher Name Bentham Science Publisher	Online ISSN 2212-4063

Cardiovascular & Hematological Disorders-Drug Targets

In silico Evaluation of ACE2 Inhibition by Prunus armeniaca L. and in vivo Toxicity Study

Abstract

Graphical Abstract

Related Journals

Related Books

Related Articles