Author(s): Emilia Tungary, Jeremi Ongko, Johan Sukweenadhi, Yulanda Antonius


DOI: 10.52711/0974-360X.2022.00712   

Address: Emilia Tungary, Jeremi Ongko, Johan Sukweenadhi, Yulanda Antonius
Faculty of Biotechnology, University of Surabaya, Surabaya, Indonesia.
*Corresponding Author

Published In:   Volume - 15,      Issue - 9,     Year - 2022

Coronavirus disease known as COVID-19 is a global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). SARS-CoV-2 binds to the receptor binding-domain of ACE-2. By blocking it with a specific ligand, we can prevent SARS-CoV-2 binding and therefore prevent its cellular entry and injury. The number of COVID-19 cases is still increasing and yet only 2.5% of Indonesians are fully vaccinated. Moreover, up to now, a specific cure for COVID-19 has not been found yet. However, many traditional medicinal plants have the potency of becoming COVID-19 drugs. Therefore, this study aimed to examine various active compounds derivate from the traditional medicinal plant as an inhibitor of SARS-CoV-2 receptor in human cell termed as ACE2. The activity and drug-likeness of the active compounds were predicted and molecular docking were conducted to identify the interactions between ligands and ACE-2. Toxicity assay was also identified to predict the toxicity class, lethal dose, and organ toxicity. This study showed that indirubin has lower binding energy as compared to the sulabiroins A and MLN-4760 as comparative control and potent inhibitor control, respectively. Indirubin shared similar interaction with amino acid residue to ACE-2 as compared to control. Based on the research result, it was suggested that Indirubin could be developed as a promising compound for COVID-19 antiviral drugs.

Cite this article:
Emilia Tungary, Jeremi Ongko, Johan Sukweenadhi, Yulanda Antonius. Molecular Docking of Active Compounds from Traditional Medicinal Plants as ACE-2 protein (1R4L) inhibitor in searching for COVID-19 drug. Research Journal of Pharmacy and Technology. 2022; 15(9):4235-0. doi: 10.52711/0974-360X.2022.00712

Emilia Tungary, Jeremi Ongko, Johan Sukweenadhi, Yulanda Antonius. Molecular Docking of Active Compounds from Traditional Medicinal Plants as ACE-2 protein (1R4L) inhibitor in searching for COVID-19 drug. Research Journal of Pharmacy and Technology. 2022; 15(9):4235-0. doi: 10.52711/0974-360X.2022.00712   Available on:

1.    Jain RS, Awad BB, Patil SB, Patil PA, Karnawat DR. Review on coronavirus its different types. Asian Journal of Pharmaceutical Research 2020; 10(2): 115-123. doi: 10.5958/2231-5659.2020.00022.3
2.    Andersen KG. Rambaut A. Lipkin WI. Holmes EC. Garry RF. The proximal origin of SARS-CoV-2. Nat. Med. 2020; 26(4):450-455.
3.    Jan H. Faisal S. Khan A. Khan S. Usman H. Liaqat R. Shah SA. COVID-19: Review of epidemiology and potential treatments against 2019 novel coronavirus. Discoveries (Craiova) 2020; 8(2):e108.
4.    Naresh BV. A review of the 2019 novel coronavirus (COVID-19) pandemic. Asian Journal of Pharmaceutical Research 2020; 10(3): 233-238. doi: 10.5958/2231-5691.2020.00040.4
5.    Starr TN. Greaney AJ. Hilton SK. Ellis D. Crawford KHD. Dingens AS. Navarro MJ. Bowen JE. Tortorici MA. Walls AC. King NP. Veesler D. Bloom JD. Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding. Cell 2020; 182(5):1295-1310.e20.  
6.    Dewangan V, Sahu R, Stapathy T, Roy A. The exploring of current development status and the unusual symptoms of Coronavirus pandemic (COVID-19). Research Journal of Pharmacology and Pharmacodynamics 2020; 12(4): 172-176. doi: 10.5958/2321-5836.2020.00031.2
7.    Ghogare RD, Navale AS, Shaikh SB. Novel corona virus: one biological disaster of 2020. Research Journal of Science and Technology 2020; 12(2): 147-156. doi: 10.5958/2349-2988.2020.00019.4
8.    Planas D. Veyer D. Baidaliuk A. Staropoli I. Guivel-Benhassine F. Rajah MM. Planchais C. Porrot F. Robillard N. Puech J. Prot M. Gallais F. Gantner P. Velay A. Le Guen J. Kassis-Chikhani N. Edriss D. Belec L. Seve A. Courtellemont L. Péré H. Hocqueloux L. Fafi-Kremer S. Prazuck T. Mouquet H. Bruel T. Simon-Lorière E. Rey FA. Schwartz O. Reduced sensitivity of SARS-CoV-2 variant delta to antibody neutralization. Nature 2021. Epub ahead of print.
9.    Conti P. Caraffa A. Gallenga CE. Kritas SK. Frydas I. Younes A. Di Emidio P. Tetè G. Pregliasco F. Ronconi G. The British variant of the new coronavirus-19 (Sars-Cov-2) should not create a vaccine problem. J Biol Regul Homeost Agents 2021; 35(1):1-4.
10.    Ghogare RD, Navale AS, Shaikh SB. Novel corona virus: One biological disaster of 2020. Research Journal of Science and Technology 2020; 12(2): 147-156. doi: 10.5958/2349-2988.2020.00019.4
11.    G Mostafa-Hedeab G. ACE2 as drug target of covid-19 virus treatment, simplified update review. Reports Biochem Molecular Bio 2020; 9(1): 97-105.
12.    Worldometers. Covid 19 coronavirus pandemic. 2021 available on
13.    Github. Covid-19-data. 2021 available on vaccinations.csv
14.    Beigel JH. Tomashek KM. Dodd LE. Mehta AK. Zingman BS. Kalil AC. Hohmann E. Chu HY. Luetkemeyer A. Kline S. Lopez de Castilla D. Finberg RW. Dierberg K. Tapson V. Hsieh L. Patterson TF. Paredes R. Sweeney DA. Short WR. Touloumi G. Lye DC. Ohmagari N. Oh M. Ruiz-Palacios GM. Benfield T. Fätkenheuer G. Kortepeter MG. Atmar RL. Creech CB. Lundgren J. Babiker AG. Pett S. Neaton JD. Burgess TH. Bonnett T. Gresn M. Makowski M. Osinusi A. Nayak S. Lane HC. Remdesivir for the treatment of Covid-19 — Preliminary report. N. Engl. J. Med. 2020; 383(19): 1813-1826.
15.    Ghasemiyeh P. Mohammadi-Samani S. COVID-19 outbreak: challenges in pharmacotherapy based on pharmacokinetic and pharmacodynamic aspects of drug therapy in patients with moderate to severe infection. Heart Lung 2020; 49(6):763-773.
16.    Yadav AR, and Mohite SK. A novel approach for treatment of COVID-19 with convalescent plasma. Research Journal of Pharmaceutical Dosage Forms and Technology 2020; 12(3): 227-230. doi: 10.5958/0975-4377.2020.00037.3
17.    Zhang QW. Lin LG. Ye WC. Technique for extraction and isolation of natural products: a comprehensive review. Chin Med 2018; 13(1):1-26.
18.    Shankhdhar PK, Mishra P, Kannojia P, Joshi H. Turmeric: plant immunobooster against COVID-19. Research Journal of Pharmacognosy and Phytochemistry 2020; 12(3): 174-177. doi: 10.5958/0975-4385.2020.00029.1
19.    Khayrani AC. Irdiani R. Aditama R. Pratami DK. Lischer K. Ansari MJ. Chinnathambi A. Alharbi SA. Almoallim HS. Sahlan M. Evaluating the potency of sulawesi propolis compounds as ACE-2 inhibitors through molecular docking for COVID-19 drug discovery preliminary study. J. King Saud University 2021; 33(2): 101297.
20.    Güller HI. Tatar G. Yildiz O. Belduz AO. Kolayli S. Investigation of ethanolic propolis extracts: their potential inhibitor properties against ACE-II receptors for COVID-19 treatment by molecular docking study. Archives of Microbio 2021.
21.    Towler P. Staker B. Prasad SG. Menon S. Tang J. Parsons T. Pantoliano MW. ACE2 X-Ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. J. Biological Chemistry 2004; 279(17): 17996-18007.
22.    Pettersen EF. Goddard TD. Huang CC. Couch GS. Greenblatt DM. Meng EC. Ferrin TE. UCSF Chimera - A visualization system for exploratory research and analysis. J. Comput. Chem. 2004; 25(13): 1605-1612.
23.    Dallakyan S. Olson AJ. Small-molecule library screening by docking with Pyrx. Methods Mol Biol 2015; 1263:243-250.
24.    Kumar RS, Basha SN, Nallasivan PK, Solomon WDS, Venkatnarayanan R. Computer aided docking studies on antiviral drugs for bird flu. Asian Journal of Research in Chemistry 2010; 3(2): 370-373.
25.    Laskowski RA. Swindells MB. LigPlot+: Multiple ligand protein interaction diagrams for drug discovery. J. Chem. Inf. Model. 2011; 51(10): 2778-2786.
26.    Daina A. Michielin O. Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 2017; 7(10):1-13.
27.    Limpinski CA. Lead-and-drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol 2004; 1(4):337-341.
28.    Banerjee P. Eckert AO. Schrey AK. Preissner R. ProTox-II: a webserver for the prediction of toxicity of chemicals. NAR 2018; 46: W257.
29.    Li Y. Zhou W. Yang L. You R. Physiological and pathological regulation of ACE2, the SARS-CoV-2 receptor. Pharmacological Research 2020; 157: 104833.
30.    Verdecchia P. Cavallini C. Spanevello A. Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. European J Internal Med 2020; 76:14-20.
31.    Gupta R. The management of coronavirus pandemic 2019-2020. Asian Journal of Pharmaceutical Research 2020; 10(4): 327-330. doi: 10.5958/2231-5691.2020.00056.8
32.    Nguyen NT. Nguyen TH. Pham TNH. Huy NT. Bay MV. Pham MQ. Nam PC. Vu VV. Ngo ST. Autodock [sic] Vina adopts more accurate binding pose but Autodock4 [sic] forms better binding affinity. J Chem Inf Model 2019; 60(1): 204-211.
33.    Khanmohammadi A. Theoritical study of various solvents effect on 5-fluorouracil-vitamin B3 complex using PCM method. J Chil Chem Soc 2019; 64(1).
34.    Upgade A, Faldu N, Kaleeswaran B. In silico analysis of non-structural protein (NS4b) from DENV-2 Indian strain for antiviral drug discovery. Research Journal of Pharmacy and Technology 2018; 11(4): 1671-1676. doi: 10.5958/0974-360X.2018.00311.6
35.    Pantsar T, and Poso A. Binding affinity via docking: Fact and fiction. Molecules 2018; 23(8): 1899. Doi: 10.3390/molecules23081899
36.    Guy JL. Jackson RM. Jensen HA. Hooper NM. Turner AJ. Identification of critical active-site residues in angiotensin-converting enzyme-2 (ACE2) by site-directed mutagenesis. FEBS Journal 2005; 272(2): 3512-3520.
37.    Nakamura Y, Asahi H. Altaf-Ul-Amin M. Kurokawa K. Kanasya S. Knapsack: Metabolite information. 2021 available on
38.    Neto-Neves EM. Montenegro MF. Dias-Junior CA. Spiller F. Kanashiro A. Tanus-Santos JE. Chronic treatment with quercetin does not inhibit Angiotensin-converting enzyme in vivo or in vitro. Basic & Clinical Pharmacology & Toxicology 2010; 107(4): 825-829.
39.    Doak BC. Over B. Giordanetto F. Kihlberg J. Oral druggable space beyond the rule of 5: insights from drugs and clinical candidates. Chem Bio 2014; 21(9): 1115-1142.
40.    Giménez BG. Santos MS. Ferrarini M. Fernandes JPS. Evaluation of blockbuster drugs under the Rule-of-five. Pharmazie 2010; 65(2): 148-152.
41.    Chavan AB, Jadhav PS, Shelke S. COVID-19: Outbreak, structure and current therapeutic strategies.Asian Journal of Pharmacy and Technology 2021; 11(1): 76-83. doi: 10.5958/2231-5713.2021.00013.1

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