scholarly journals Single bulb garlic organosulfur compounds in inhibiting angiotensin-converting enzyme (ACE) as hypertension therapeutic strategies: An in silico study

2021 ◽  
Author(s):  
Nurul Ahillah ◽  
Sri Rahayu Lestari ◽  
Abdul Gofur
Keyword(s):  
Angiotensin Converting Enzyme ◽  
In Silico ◽  
Therapeutic Strategies ◽  
Organosulfur Compounds ◽  
Converting Enzyme ◽  
In Silico Study

scholarly journals Screening Virtual ACE2 Enzyme Inhibitory Activity of Compounds for COVID-19 Treatment Based on Molecular Docking

2020 ◽  
Vol 36 (4) ◽  
Author(s):  
Bui Thanh Tung ◽  
Phạm Hong Minh ◽  
Nguyen Nhu Son ◽  
Pham The Hai
Keyword(s):  
New York ◽  
Molecular Docking ◽  
Angiotensin Converting Enzyme ◽  
Inhibitory Activity ◽  
In Silico ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Angiotensin Converting Enzyme 2 ◽  
In Silico Study ◽  
Novel Coronavirus

This study uses an in silico screening docking model to evaluate the ACE2 inhibitory activity of natural compounds and drugs. The study collected 49 compounds and evaluated the ACE2 inhibitory effect in silico. The study results show that 11 out of the 49 compounds had stronger inhibitory activity on ACE2 than MLN-4760. Lipinski’s rule of five criteria and predictive pharmacokinetic-toxicity analysis show that eight compounds including quercetin, galangin, quisinostat, fluprofylline, spirofylline, RS 504393, TNP and GNF-5 had drug-likeness. These compounds could be potential drug for the Covid-19 treatment. Keywords SARS-CoV-2S, Covid-19, ACE2, molecular docking, in silico. References [[1] C. Wang, P.W. Horby, F.G. Hayden, G.F. Gao. A novel coronavirus outbreak of global health concern. The Lancet 395(10223) (2020) 470.[2] WHO. WHO Coronavirus Disease (COVID-19) Dashboard. WHO, 2020.[3] N. Chen, M. Zhou, X. Dong, J. Qu, F. Gong, Y. Han, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet 395(10223) (2020) 507.[4] J. Yang, Y. Zheng, X. Gou, K. Pu, Z. Chen, Q. Guo, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. International Journal of Infectious Diseases 94 (2020) 91.[5] R. Lu, X. Zhao, J. Li, P. Niu, B. Yang, H. Wu, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet 395(10224) (2020) 565.[6] R. Hilgenfeld. From SARS to MERS: crystallographic studies on coronaviral proteases enable antiviral drug design. The FEBS journal 281(18) (2014) 4085.[7] D. Wrapp, N. Wang, K.S. Corbett, J.A. Goldsmith, C.L. Hsieh, O. Abiona, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science (New York, NY) 367(6483) (2020) 1260.[8] P.A. Rota, M.S. Oberste, S.S. Monroe, W.A. Nix, R. Campagnoli, J.P. Icenogle, et al. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science (New York, NY) 300(5624) (2003) 1394.[9] M. Donoghue, F. Hsieh, E. Baronas, K. Godbout, M. Gosselin, N. Stagliano, et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circulation research 87(5) (2000) E1.[10] H. Zhang, Z. Kang, H. Gong, D. Xu, J. Wang, Z. Li, et al. The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes. bioRxiv (2020) 2020.01.30.927806.[11] Y. Zhao, Z. Zhao, Y. Wang, Y. Zhou, Y. Ma, W. Zuo. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. bioRxiv (2020) 2020.01.26.919985.[12] E.I. Bahbah, A. Negida, M.S. Nabet. Purposing Saikosaponins for the treatment of COVID-19. Med Hypotheses 140 (2020) 109782.[13] I.W. Cheung, S. Nakayama, M.N. Hsu, A.G. Samaranayaka, E.C. Li-Chan. Angiotensin-I converting enzyme inhibitory activity of hydrolysates from oat (Avena sativa) proteins by in silico and in vitro analyses. Journal of agricultural and food chemistry 57(19) (2009) 9234.[14] T. Joshi, T. Joshi, P. Sharma, S. Mathpal, H. Pundir, V. Bhatt, et al. In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking. European review for medical and pharmacological sciences 24(8) (2020) 4529.[15] S. Shahid, A. Kausar, M. Khalid, S. Tewari, T. Alghassab, T. Acar, et al. analysis of binding properties of angiotensin-converting enzyme 2 through in silico molecular docking, 2018.[16] K. Teralı, B. Baddal, H.O. Gülcan. Prioritizing potential ACE2 inhibitors in the COVID-19 pandemic: Insights from a molecular mechanics-assisted structure-based virtual screening experiment. J Mol Graph Model 100 (2020) 107697.[17] M. Muchtaridi, M. Fauzi, N.K. Khairul Ikram, A. Mohd Gazzali, H.A. Wahab. Natural Flavonoids as Potential Angiotensin-Converting Enzyme 2 Inhibitors for Anti-SARS-CoV-2. Molecules 25(17) (2020) 3980.[18] M.J. Huentelman, J. Zubcevic, J.A. Hernández Prada, X. Xiao, D.S. Dimitrov, M.K. Raizada, et al. Structure-based discovery of a novel angiotensin-converting enzyme 2 inhibitor. Hypertension (Dallas, Tex : 1979) 44(6) (2004) 903.[19] S. Choudhary, Y.S. Malik, S. Tomar. Identification of SARS-CoV-2 Cell Entry Inhibitors by Drug Repurposing Using in silico Structure-Based Virtual Screening Approach. Front Immunol 11((2020) 1664.[20] C.A. Lipinski. Lead-and drug-like compounds: the rule-of-five revolution. Drug Discovery Today: Technologies 1(4) (2004) 337.[21] B. Jayaram, T. Singh, G. Mukherjee, A. Mathur, S. Shekhar, V. Shekhar, Eds. Sanjeevini: a freely accessible web-server for target directed lead molecule discovery. Proceedings of the BMC bioinformatics; 2012. Springer (Year).[22] D.E. Pires, T.L. Blundell, D.B. Ascher. pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of medicinal chemistry 58(9) (2015) 4066.[23] P. Towler, B. Staker, S.G. Prasad, S. Menon, J. Tang, T. Parsons, et al. ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. The Journal of biological chemistry 279(17) (2004) 17996.[24] N.A. Dales, A.E. Gould, J.A. Brown, E.F. Calderwood, B. Guan, C.A. Minor, et al. Substrate-based design of the first class of angiotensin-converting enzyme-related carboxypeptidase (ACE2) inhibitors. Journal of the American Chemical Society 124(40) (2002) 11852.[25] P. Pandey, J.S. Rane, A. Chatterjee, A. Kumar, R. Khan, A. Prakash, et al. Targeting SARS-CoV-2 spike protein of COVID-19 with naturally occurring phytochemicals: an in silico study for drug development. Journal of Biomolecular Structure and Dynamics (2020) 1.[26] C.A. Lipinski. Lead- and drug-like compounds: the rule-of-five revolution. Drug discovery today Technologies 1(4) (2004) 337.[27] R.O. Barros, F.L. Junior, W.S. Pereira, N.M. Oliveira, R.M. Ramos. Interaction of drug candidates with various SARS-CoV-2 receptors: An in silico study to combat COVID-19. Journal of Proteome Research (2020).  

scholarly journals In silico study of potential anti-SARS cell entry phytoligands from Phlomis aurea: a promising avenue for prophylaxis

2021 ◽  
Author(s):  
Amira R Khattab ◽  
Mohamed Teleb ◽  
Mohamed S Kamel
Keyword(s):  
Angiotensin Converting Enzyme ◽  
In Silico ◽  
Protective Role ◽  
Cell Entry ◽  
Health Concern ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
In Silico Study ◽  
Promising Avenue

Aim: The severity of COVID-19 has raised a great public health concern evoking an urgency for developing multitargeted therapeutics. Phlomis species was ethno-pharmacologically practiced for respiratory ailments. Materials & methods: An array of 15 phytoligands previously isolated from Phlomis aurea were subjected to molecular docking to explore their potential SARS-CoV-Spike-angiotensin-converting enzyme 2 complex inhibition, that is essential for virus entry to host cell. Results: Acteoside (11) showed the most potent in silico inhibition with an additional merit, over hesperidin (16), of not binding to angiotensin-converting enzyme 2 with well proven in vivo pulmonary protective role in acute lung injury, followed by chrysoeriol-7- O-β-glucopyranoside (12) and luteolin-7- O-β-glucopyranoside (14). Conclusion: Phytoligands (11, 12 and 14) were posed as promising candidates with potential prophylactic action against COVID-19. These phytoligands were prioritized for further biological experimentation because of their acceptable predicted ADME and drug-likeness parameters. Moreover, they could aid in developing multitargeted strategy for better management of COVID-19 using phytomedicines.

scholarly journals Mengidentifikasi Peptida Bioaktif Angiotensin Converting Enzyme-inhibitor (ACEi) dari Kasein β Susu Kambing dengan Polimorfismenya Melalui Teknik In Silico

2019 ◽  
Vol 7 (4) ◽  
Author(s):  
Hermawan Setyo Widodo ◽  
Tridjoko Wisnu Murti ◽  
Ali Agus ◽  
Widodo Widodo
Keyword(s):  
Angiotensin Converting Enzyme ◽  
In Silico ◽  
Digestive Enzymes ◽  
Bioactive Peptides ◽  
Enzyme Inhibitor ◽  
Goat Milk ◽  
Bioactive Peptide ◽  
Converting Enzyme ◽  
Lipinski’S Rule ◽  
Lipinski’S Rule Of Five

Susu kambing memiliki komponen protein salah satunya protein β dan secara umum terjadi polimorfisme pada level protein. Perubahan urutan asam amino akibat polimorfisme memungkinkan adanya potensi dihasilkannya peptida bioaktif penghambat enzim pengubah angiotensin (ACEi). Penelitian ini bertujuan untuk menyaring peptida bioaktif yang berpotensi sebagai ACEi dari kasein β kambing beserta polimorfismenya. Penelitian ini dilakukan dengan teknik in silico terhadap sekuen kasein β kambing serta struktur tiga dimensi human testicular ACE. Langkah yang dilakukan dalam penelitian ini meliputi simulasi pemotongan peptida dengan enzim pencernaan (pepsin, tripsin dan kimotripsin), peninjauan karakteristik peptida lalu simulasi docking ligan-reseptor. Tampilan parameter Lipinski’s Rule of Five (Ro5), bioaktivitas dan energi afinitas dipertimbangkan untuk memilih peptida bioaktif. Hasil yang didapat menunjukkan bahwa ditemukan peptida bioaktif yakni INK (Ile-Asp-Lys) yang memiliki kemampuan hampir setara dengan lisinopril (afinitas energi -8,2kkal/mol vs. -8,3kkal/mol). Peptida INK dapat ditemukan dari hasil hidrolisis dari alel A, C, D dan E, sehingga polimorfisme tidak menyebabkan perbedaan produksi peptida bioaktif. Kesimpulan yang dapat diambil yakni kasein β susu kambing jika dicerna dengan enzim pencernaan dapat menghasilkan peptida bioaktif ACEi yakni INK.Identification of Angiotensin Converting Enzyme-inhibitor (ACEi) Bioactive Peptide from Goat Milk β-Casein with It's Polymorphism by In Silico TechniqueAbstractPolymorphism eventually may be occurred at the protein level. Changes in the amino acid sequence due to polymorphism may exhibit a potential action to generate of the angiotensin-converting enzyme inhibitors (ACEi) bioactive peptide. This study is aimed to assess bioactive peptides that have a great potent value as ACEi from goat β casein along with its polymorphism. The research was done by in silico technique on goat β-casein sequence and three-dimensional structure human testicular ACE. Peptide-cutting simulations with digestive enzymes (pepsin, trypsin and chymotrypsin), peptide properties review, then ligand-receptor docking simulations was applied in this research. Appearance of Lipinski's Rule of Five (Ro5), bioactivity and affinity energy were considered for selecting bioactive peptides. The results show that bioactive peptide found as INK (Ile-Asp-Lys) which had similar ability as lisinopril (energy affinity –8.2kcal/mol vs. –8.3kcal/mol). The INK peptides could be found from the hydrolysis resulted in alleles A, C, D and E, therefore polymorphism did not affect the differences of production of bioactive peptides. A conclusion, processed goat milk β casein with digestive enzymes could produce ACEi of INK as bioactive peptide.

scholarly journals Pathways and microRNAs bioinformatics analyses identifying possible existing therapeutics for COVID-19 treatment

2020 ◽  
Author(s):  
Laura Teodori ◽  
Piero Sestili ◽  
Valeria Madiai ◽  
Sofia Coppari ◽  
Daniele Fraternale ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
In Silico ◽  
Molecular Mechanisms ◽  
Hdac Inhibitors ◽  
Converting Enzyme ◽  
Bioinformatics Analyses ◽  
Off Label ◽  
Host Virus Interactions ◽  
Virus Interactions ◽  
Ranked List

Abstract Over 180.000 SARS-COV-2 positive cases have been confirmed in Italy as April 20, with the number of deaths exceeding 23 thousand, making Italy the second Country for world COVID-19 deaths. Such enormous occurrence of infected and dead people raises the urgent demand of effective fast available treatments to control and diminish this pandemic. Discovering the cellular/molecular mechanisms of SARS-COV-2 pathogenicity is of paramount importance to understand how the infection becomes a disease and for therapeutically approaching it. From literature data, through a bioinformatics approach, an in silico analysis was performed, to predict the putative virus targets and evidence the already available therapeutics. Literature experimental results identified angiotensin-converting enzyme ACE and Spike proteins particularly involved in COVID-19. We thus investigate on the signaling pathways modulated by the two proteins through query miRNet, the platform linking miRNAs, targets and functions. We predicted microRNAs (miRs), miR-335-5p and miR-26b-5p, as being modulated by Spike and ACE together with deacetylate histones pathway HDAC. Our results matched with the available clinical data. We hypothesize the current and EMA-approved, SARS-COV-2 off-label, HDAC inhibitors (HDACis) drugs may be repurposed to limit or block host-virus interactions. A ranked list of compounds is given that can be tested.

scholarly journals Virtual Screening Peptida Bioaktif Antihipertensi dari Hidrolisat Kasein Susu Kambing Etawa

ALCHEMY ◽  
2016 ◽  
Vol 5 (2) ◽  
pp. 45
Author(s):  
Sandra Hermanto
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Angiotensin Converting Enzyme ◽  
Protease Inhibitor ◽  
In Silico ◽  
Reference Sequence ◽  
Capra Hircus ◽  
Converting Enzyme

Penapisan peptida bioaktif dari hidrolisat kasein susu kambing Etawa yang berpotensi sebagai obat antihipertensi berdasarkan kajian <em>in silico </em>telah dilakukan. Protein yang digunakan adalah α-S1-kasein prekursor [<em>Capra hircus</em>] NCBI <em>Reference Sequence</em>: NP_001272624.1, α-S2-kasein prekursor [<em>C. hircus</em>] NCBI <em>Reference Sequence</em>: NP_001272514.1, β-kasein [<em>C. hircus</em>] NCBI <em>Reference Sequence</em>: AAA30906.1 dan κ-kasein prekursor [<em>C. hircus</em>] NCBI <em>Reference Sequence</em>: NP_001272516.1. Perancangan struktur peptida bioaktif dilakukan melalui simulasi hidrolisis enzimatik dengan menggunakan 3 jenis enzim proteolitik (tripsin, kimotripsin dan pepsin) dan dilanjutkan dengan preparasi struktur 3D ligan hasil pemotongan secara <em>in silico</em>. <em>Virtual screening</em> terhadap fragmen peptida dilakukan melalui penentuan nilai <em>drug likeness</em> dan <em>protease inhibitor.</em> Dari 104 fragmen peptida diperoleh 10 kandidat peptida bioaktif yang dilakukan simulasi <em>molecular docking</em> dengan mengeksplorasi daya inhibisi fragmen melalui perhitungan nilai (∆<em>G<sub>binding</sub></em>) dan interaksi antara kandidat peptida bioaktif dengan residu asam amino pada sisi aktif enzim ACE (<em>Angiotensin Converting Enzyme)</em>. Sebagai kontrol positif digunakan lisinopril yang merupakan inhibitor ACE komersil. Hasil penelitian menunjukkan dari 10 kandidat peptida bioaktif terdapat 6 peptida yang diduga bersifat antihipertensi dengan nilai ∆<em>G<sub>binding</sub></em><em></em><sub> </sub>yang lebih rendah dari kontrol positif (lisinopril). Keenam peptida tersebut diharapkan dapat berfungsi sebagai obat alternatif antihipertensi.

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