In Silico Screening of Potential Essential Oil of Mentha Pipperita

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In Silico Screening of Potential Essential Oil of Mentha pipperita and Cymbopogon citratus Agnaist Covid-19 by Targeting Angiotensin- Converting Enzyme 2 (ACE2) and Aminopeptidase (APN): Molecular Docking Approach Yoni Rina Bintari, Dini Sri Damayanti Faculty of Medicine, University of Islamic Malang, Indonesia Coresponding Author : [email protected] Introduction Results Table 1. Inhibiting potency of essentian oil from M. pipperita and C. citratus against ACE 2 ❑ COVID-19 is a type of disease caused by a virus from the coronavirus class, Protein Binding Affinity namely SARS-CoV-2. This disease is becoming a pandemic, which needs Plant Active Compound CID Reseptor (kcal/mol) solution. M. pipperita menthol 1254 APN -5 ❑ Mechanism of corova virus infection is is initiated by interaction of the viral metil acetat 6584 APN -3.7 particle with specific proteins on the cell surface. Receptor proteins that can methofuran 329983 APN -5.9 be bound by the coronavirus genera include Aminopeptidase (APN) and Carvone 7439 APN -5.2 menthol 1254 ACE II -5.1 Angiostensin-Converting Enzyme 2 (ACE 2) [1][2] metil acetat 6584 ACE II -3.3 ❑ Essential oil of Mentha pipperita has antiviral activity against the respiratory methofuran 329983 ACE II -6.7 syncytial virus (RSV) and the anti-inflammatoryactivity were evaluated in Carvone 7439 ACE II -6.8 Cimbopogon Citronela 7794 APN -4.8 vitro. [3] citratus ❑ Essential oil Cymbopogon citratus has antiviral activity agnaist human Geranyl acetat 1549026 APN -5.7 mastadenovirus serotype [4] Patchuoli alkohol 10955174 APN -6.9 Citronela 7794 ACE II -5.6 Geranyl acetat 1549026 ACE II -6.3 Pachuoli alkohol 10955174 ACE II -6.9 Control Captopril 44093 ACE II -5.4 Chloroquine 2719 ACE II -4.9 Captopril 44093 APN -5.8 Chloroquine 2719 APN -6

Table 2. Hydrogen binding ligan and protein receptor Figure 1. Spike proteins on the surface of the coronavirus bind to angiotensin-converting enzyme 2 (ACE- No Active Compound Protein Receptor Hydrogen Binding 2) receptors on the surface of the target cell [1] 1 Menthofuran ACE II - 2 Menthol ACE II - 3 Methyl acetat ACE II Lys 353; Gli 354; Arg 393; 4 Carvone ACE II Trp 566 Objectives 5 Patchuoli alkohol ACE II 6 Citronela ACE II Glu 435;Thr 434 This study aims to screen the essential oil of M. pipperita and C. citratus using 7 Captoril* ACE II Arg 482; Glu 489; His 493; Tyr 613 a molecular docking approach by inhibiting the attachment and entry process 8 Kloroquine* ACE II - through the ACE 2 receptor protein (Q9BYF1) and APN (P15144). 9 Menthofuran APN Ser 701 10 Menthol APN - 11 Methyl acetat APN Val 822; Asn 823 12 Carvone APN Ser 758; Thr 759 Methods 13 Patchuoli alkohol APN Asn 667; Ser 701 14 Citronela APN Asn 663; Ser 701 15 Captoril* APN Arg 631; Asn 663; Asn 667 Ligand preparation: 16 Kloroquine* APN Arg 631; Asn 663; Asn 668 The structure of 3D essential oil of M.pipperita and C. *Control citratus; control compounds (chloroquine and catopril) was downloaded from the PubChem server (https://pubchem.ncbi.nlm.nih.gov)

Receptor Preparation: Figure 1. ACE 2 protein reseptor APN (P15144) and ACE 2 (Q9BYF1) was downloaded from the server Protein Data Bank (https://www.rcsb.org/). The protein obtained was downloaded and stored in the .pdb

format. a b c Figure 3. Interaction between ligand with APN protein receptor; (a) Patchuoli alcohol; (b) captopril; (c)kloroquine Molecular Docking: The docking process is carried out using the AutoDock Vina with PyRx program. The ligand from the docking Discussion process (ligand validation) was stored and a comparison with the control ligand to see the value of root-mean- ❑ Essential oil of C. citratus has potential antiviral activity. The active compound is patchouli alkohol square deviation (RMSD). Docking software is preferred to predict results from experimental positions with RMSD no ❑ Predicted, patchouli alcohol can inhibit Asn 667 and Ser 701 of APN with hydrogen bond more than 2.0 Å. The docking results are then visualized ❑ Patchuoli acohol has lower binding energy than control. using the PyMol program. To see the interaction between receptors and ligands using the Biovia Discovery Studio program. Figure 2. APN protein reseptor Conclusion

❑ Studi in vitro anti Covid 19 activity essential oil to be studied further for complete understanding and confirmation of their inhibitory potential References

[1] Sandrine Belouzard 1, Jean K. Millet 2, Beth N. Licitra 2 and Gary R. Whittaker. 2014. Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein. Viruses: 4, 1011-1033

[2] Zofia Wicik, Ceren Eyileten, Daniel Jakubik, Rodrigo Pavão, Jolanta M. Siller-Matula, Marek Postula. 2020. ACE2 interaction networks in COVID-19: a physiological framework for prediction of outcome in patients with cardiovascular risk factors

[3] YuXian Li1, YiBo Liu, AiQin Ma, Yong Bao5, Man Wang4, ZhenLiang Sun. 2017. In vitro antiviral, anti-inflammatory, and antioxidant activities of the ethanol extract of Mentha piperita L. Food Sci Biotechnol: 26(6):1675–1683

[4] Lisandra Chiamenti1*, Francini Pereira da Silva2, Karoline Schallemberger3, Meriane Demoliner4, Caroline Rigotto5, Juliane Deise Fleck. 2019. Cytotoxicity and antiviral activity evaluation of Cymbopogon spp hydroethanolic extracts. Braz. J. Pharm. Sci. 2019;55:e18063