scholarly journals The Identification of Novel Inhibitors of Human Angiotensin-converting Enzyme 2 and Main Protease of Sars-Cov-2: A Combination of in silico Methods for Treatment of COVID-19

2021 ◽  
pp. 130409
Author(s):  
Vahid Zarezade ◽  
Hamzeh Rezaei ◽  
Ghodratollah Shakerinezhad ◽  
Arman Safavi ◽  
Zahra Nazeri ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
In Silico ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Main Protease ◽  
In Silico Methods

scholarly journals A Multifunctional Peptide From Bacillus Fermented Soybean for Effective Inhibition of SARS-CoV-2 S1 Receptor Binding Domain and Modulation of Toll Like Receptor 4: A Molecular Docking Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Srichandan Padhi ◽  
Samurailatpam Sanjukta ◽  
Rounak Chourasia ◽  
Rajendra K. Labala ◽  
Sudhir P. Singh ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Angiotensin Converting Enzyme ◽  
Receptor Binding ◽  
In Silico ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Angiotensin Converting Enzyme 2 ◽  
Fermented Soybean

Fermented soybean products are traditionally consumed and popular in many Asian countries and the northeastern part of India. To search for potential agents for the interruption of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike glycoprotein 1 (S1) and human angiotensin-converting enzyme 2 (ACE2) receptor interactions, the in silico antiviral prospective of peptides identified from the proteome of kinema was investigated. Soybean was fermented using Bacillus licheniformis KN1G, Bacillus amyloliquefaciens KN2G and two different strains of Bacillus subtilis (KN2B and KN2M). The peptides were screened in silico for possible antiviral activity using two different web servers (AVPpred and meta-iAVP), and binding interactions of selected 44 peptides were further explored against the receptor-binding domain (RBD) of the S1 protein (PDB ID: 6M0J) by molecular docking using ZDOCK. The results showed that a peptide ALPEEVIQHTFNLKSQ (P13) belonging to B. licheniformis KN1G fermented kinema was able to make contacts with the binding motif of RBD by blocking specific residues designated as critical (GLN493, ASN501) in the binding of human angiotensin-converting enzyme 2 (ACE2) cell receptor. The selected peptide was also observed to have a significant affinity towards human toll like receptor 4 (TLR4)/Myeloid Differentiation factor 2 (MD2) (PDB ID: 3FXI) complex known for its essential role in cytokine storm. The energy properties of the docked complexes were analyzed through the Generalized Born model and Solvent Accessibility method (MM/GBSA) using HawkDock server. The results showed peptidyl amino acids GLU5, GLN8, PHE11, and LEU13 contributed most to P13-RBD binding. Similarly, ARG90, PHE121, LEU61, PHE126, and ILE94 were appeared to be significant in P13-TLR4/MD2 complex. The findings of the study suggest that the peptides from fermented soy prepared using B. licheniformis KN1G have better potential to be used as antiviral agents. The specific peptide ALPEEVIQHTFNLKSQ could be synthesized and used in combination with experimental studies to validate its effect on SARS-CoV-2-hACE2 interaction and modulation of TLR4 activity. Subsequently, the protein hydrolysate comprising these peptides could be used as prophylaxis against viral diseases, including COVID-19.

scholarly journals Structure-Based Screening of Novel Lichen Compounds for SARS Coronavirus Main protease (Mpro) and Angiotensin-Converting Enzyme 2 (ACE2) inhibitory potentials as multi-target inhibitors of COVID-19

2020 ◽  
Author(s):  
Tanuja Joshi ◽  
Priyanka Sharma ◽  
Tushar Joshi ◽  
Hemlata Pundir ◽  
Shalini Mathpal ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Antiviral Agents ◽  
Converting Enzyme ◽  
Suitable Candidate ◽  
Angiotensin Converting Enzyme 2 ◽  
Drug Candidates ◽  
Main Protease ◽  
Toxicity Analysis ◽  
Dual Inhibitors ◽  
Lichen Compounds

Abstract Outbreak of SARS-CoV-2 and massing death caused by it all over world has imposed great concern on scientific community to develop potential drugs to combat with Coronaviruas disease 19 ( COVID-19 ). In this regard, lichen metabolites may offer a vast reservoir for discovery of anti-viral drug candidates. Therefore to find novel compounds against COVID-19, we created a library of 412 lichen compounds and subjected to virtual screening against two molecular targets; SARS-CoV-2 target- Main protease (Mpro) and host cell target- Angiotensin-converting enzyme 2 (ACE2). All the ligands were virtually screened, and 80 compounds were found to have better docking score with both the targets. These compounds were assessed for druglikeness analysis where 27 compounds were found to fit well for redocking studies. The results of redocking by X-Score showed that 7 out of 27 compounds were found to have high affinities with Mpro as well ACE2 which reflect that these compounds can function as dual inhibitors. Molecular docking, druglikeness, X-Score and toxicity analysis resulting seven novel lichen compounds (Orcinyllecanorate, Siphulin, Fremontol, Gyrophoric acid, Rhizocarpic acid, Ovoic acid, and Umbilicaric acid) with Mpro and ACE2 multi-target activities and they can be used as hit compounds to develop potential antiviral agents against SARS-CoV-2. These lichen compounds may be a suitable candidate for further experimental analysis.

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).  

Potential Inhibitors Identification of Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Angiotensin-Converting Enzyme 2 and Main Protease from Anatolian Traditional Plants

2021 ◽  
Vol 19 ◽  
Author(s):  
Namık Kılınç ◽  
Mikail Açar ◽  
Salih Tuncay ◽  
Ömer Faruk Karasakal
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Chlorogenic Acid ◽  
Caffeic Acid ◽  
Rosmarinic Acid ◽  
Carnosic Acid ◽  
Binding Affinities ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Docking Simulations ◽  
Main Protease

Background: The 2019 novel coronavirus disease (COVID-19) has caused a global health catastrophe by affecting the whole human population around the globe. Unfortunately, there is no specific medication or treatment for COVID-19 currently available. Objective: It’s extremely necessary to apply effective drug treatment in order to end the pandemic period and return daily life to normal. In terms of the urgency of treatment, rather than focusing on the discovery of novel compounds, it is critical to explore the effects of existing herbal agents with proven antiviral properties on the virus. Method: Molecular docking studies were carried out with three different methods, Glide extra precision (XP) docking, Induced Fit docking (IFD), and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA), to determine the potential effects of 58 phytochemicals in the content of Rosmarinus officinalis, Thymbra spicata, Satureja thymbra, and Stachys lavandulifolia plants -have antiviral and antibacterial effects- against Main Protease (Mpro) and Angiotensin Converting Enzyme 2 (ACE2) enzymes. Results: 7 compounds stand out among all molecules by showing very high binding affinities. According to our findings, the substances chlorogenic acid, rosmarinic acid, and rosmanol exhibit extremely significant binding affinities for both Mpro and ACE2 enzymes. Furthermore, it was discovered that carnosic acid and alpha-cadinol showed potential anti-Mpro activity, whereas caffeic acid and carvacrol had promising anti-ACE2 activity. Conclusion: Chlorogenic acid, rosmarinic acid, rosmanol, carnosic acid, alpha-cadinol, caffeic acid, and carvacrol compounds have been shown to be powerful anti-SARS-COV-2 agents in docking simulations against Mpro and ACE2 enzymes, as well as ADME investigations.

scholarly journals Targeting the glycan of receptor binding domain with jacalin as a novel approach to develop a treatment against COVID-19

2020 ◽  
Vol 7 (9) ◽  
pp. 200844
Author(s):  
Senthilnathan Rajendaran ◽  
Arunchalam Jothi ◽  
Veerappan Anbazhagan
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Receptor Binding ◽  
Conformational Changes ◽  
In Silico ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Approach

In silico analysis revealed that a lectin, jacalin from jackfruit seeds, recognizes a glycosylated region of the receptor-binding domain (RBD) of SARS-CoV2. Jacalin binding induces conformational changes in RBD and significantly affects its interaction with human angiotensin-converting enzyme 2. The result may open up exploration of lectin-based strategies against COVID-19.

scholarly journals Virtual screenings of the bioactive constituents of tea, prickly chaff, catechu, lemon, black pepper, and synthetic compounds with the main protease (Mpro) and human angiotensin-converting enzyme 2 (ACE 2) of SARS-CoV-2

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Nazim Uddin Emon ◽  
Md. Munsur Alam ◽  
Irin Akter ◽  
Saima Akhter ◽  
Anjuman Ara Sneha ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Binding Affinity ◽  
Chemical Constituents ◽  
Black Pepper ◽  
Converting Enzyme ◽  
Bioactive Constituents ◽  
Synthetic Compounds ◽  
Angiotensin Converting Enzyme 2 ◽  
Discovery Studio ◽  
Main Protease

Abstract Background COVID-19 has mutation capability, and there are no specific drug therapies that are available to fight or inhibit the proteins of this virus. The present study aims to investigate the binding affinity of the bioactive and synthetic compounds with the main protease (Mpro) enzymes and angiotensin-converting enzyme 2 (ACE 2) by computational approach. PASS prediction, pharmacokinetics, and toxicological properties prediction studies were performed through the Google PASS prediction and Swiss ADME/T website. Besides, molecular docking studies were accomplished by BIOVIA Discovery Studio 2020, UCSF Chimera, and PyRx autodock vina. Results The docking scores were inferred and the selected compounds showed results varying from −3.2 to −9.8 (kcal/mol). Theaflavin scored the highest docking score to the 5REB, 6VW1, and 1R42 enzymes and showed the binding affinity as −6.3 kcal/mol, −9.8 kcal/mol, and −8.6 kcal/mol, respectively. Again, kaempferol showed the best binding affinity to the 7BQY (−7.1 kcal/mol) and 6Y2FB (−6.6 kcal/mol) enzymes. All the chemical constituents showed better probability in action in pass prediction analysis. Besides, no ligands (except theaflavin) have any conflict with Lipinski’s rules of five, which authorized the drug probability of these ligands. Conclusion Therefore, the selected compounds could be considered a potential herbal treatment source against SARS-CoV-2.

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.

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