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 Identification of novel inhibitors of Angiotensin-converting enzyme 2 (ACE-2) receptor from Urtica dioica to combat coronavirus disease 2019 (COVID-19)

2020 ◽  
Author(s):  
Shobha Upreti ◽  
Jyoti Sankar Prusty ◽  
Satish Chandra Pandey ◽  
Awanish Kumar ◽  
Mukesh Samant
Keyword(s):  
Molecular Docking ◽  
Angiotensin Converting Enzyme ◽  
Binding Affinity ◽  
Active Site ◽  
Urtica Dioica ◽  
Receptor Protein ◽  
Amino Acid Residues ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Discovery Studio

Abstract The pandemic outbreak of coronavirus (SARS-CoV-2) is rapidly spreading across the globe, so the development of anti-SARS-CoV-2 agents is urgently needed. Angiotensin-converting enzyme 2 (ACE-2), a human receptor that facilitates entry of SARS-CoV-2, serves as a prominent target for drug discovery. In the present study, we have applied the bioinformatics approach for screening of a series of bioactive chemical compounds from Himalayan stinging nettle (Urtica dioica) as potent inhibitors of ACE-2 receptor (PDB ID: 1R4L). The molecular docking was applied to dock a set of representative compounds within the active site region of target receptor protein using 0.8 version of the PyRx virtual screen tool and analyzed by using discovery studio visualizer. Based on the highest binding affinity, 16 compounds were shortlisted as a lead molecule using molecular docking analysis. Among them, β-sitosterol was found with the highest binding affinity -12.2 Kcal/mol and stable interactions with the amino acid residues present on the active site of the ACE-2 receptor. Similarly, Luteoxanthin and Violaxanthin followed by rutin also displayed stronger binding efficiency. We propose these compounds as potential lead candidates for the development of target specific therapeutic drugs against COVID-19.

scholarly journals Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin Converting Enzyme 2 Receptor

2020 ◽  
Author(s):  
Sanchita Hati ◽  
Sudeep Bhattacharyya
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Binding Affinity ◽  
Disulfide Bonds ◽  
Host Cells ◽  
Converting Enzyme ◽  
Dynamic Simulations ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus ◽  
The Impact ◽  
Spike Proteins

AbstractThe novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an ongoing pandemic of coronavirus disease (COVID-19), which started in 2019. This is a member of Coronaviridae family in the genus Betacoronavirus, which also includes SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). The angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV and SARS-CoV-2 to enter the host cells. In particular, the interaction of viral spike proteins with ACE2 is a critical step in the viral replication cycle. The receptor binding domain of the viral spike proteins and ACE2 have several cysteine residues. In this study, the role of thiol-disulfide balance on the interactions between SARS-CoV/CoV-2 spike proteins and ACE2 was investigated using molecular dynamic simulations. The study revealed that the binding affinity was significantly impaired when all the disulfide bonds of both ACE2 and SARS-CoV/CoV-2 spike proteins were reduced to thiol groups. The impact on the binding affinity was less severe when the disulfide bridges of only one of the binding partners were reduced to thiols. This computational finding provides a molecular basis for the severity of COVID-19 infection due to the oxidative stress.

scholarly journals Rapid Assessment of Binding Affinity of SARS-COV-2 Spike Protein to the Human Angiotensin-Converting Enzyme 2 Receptor and to Neutralizing Biomolecules Based on Computer Simulations

2021 ◽  
Vol 12 ◽  
Author(s):  
Damiano Buratto ◽  
Abhishek Saxena ◽  
Qun Ji ◽  
Guang Yang ◽  
Sergio Pantano ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Binding Affinity ◽  
Rapid Assessment ◽  
Cost Effective ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Spike Glycoprotein ◽  
Host Cell Membrane ◽  
Angiotensin Converting Enzyme 2 ◽  
Dynamics Simulations

SARS-CoV-2 infects humans and causes Coronavirus disease 2019 (COVID-19). The S1 domain of the spike glycoprotein of SARS-CoV-2 binds to human angiotensin-converting enzyme 2 (hACE2) via its receptor-binding domain, while the S2 domain facilitates fusion between the virus and the host cell membrane for entry. The spike glycoprotein of circulating SARS-CoV-2 genomes is a mutation hotspot. Some mutations may affect the binding affinity for hACE2, while others may modulate S-glycoprotein expression, or they could result in a virus that can escape from antibodies generated by infection with the original variant or by vaccination. Since a large number of variants are emerging, it is of vital importance to be able to rapidly assess their characteristics: while changes of binding affinity alone do not always cause direct advantages for the virus, they still can provide important insights on where the evolutionary pressure is directed. Here, we propose a simple and cost-effective computational protocol based on Molecular Dynamics simulations to rapidly screen the ability of mutated spike protein to bind to the hACE2 receptor and selected neutralizing biomolecules. Our results show that it is possible to achieve rapid and reliable predictions of binding affinities. A similar approach can be used to perform preliminary screenings of the potential effects of S-RBD mutations, helping to prioritize the more time-consuming and expensive experimental work.

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.

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 Antiviral phytochemicals identified in Rhododendron arboreum petals exhibited strong binding to SARS-CoV-2 MPro and Human ACE2 receptor

2020 ◽  
Author(s):  
Maneesh Lingwan ◽  
Shagun Shagun ◽  
Yogesh Pant ◽  
Bandna Kumari ◽  
Ranjan Nanda ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Secondary Metabolites ◽  
Angiotensin Converting Enzyme ◽  
Quinic Acid ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Rhododendron Arboreum ◽  
Strong Binding ◽  
Main Protease ◽  
Adme Properties

Background: Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) affects human respiratory function causing COVID-19 disease. Safe natural products with potential antiviral phytochemicals with benefits to control high-altitude sickness could be adopted as adjunct therapy for COVID-19. The red petals of Rhododendron arboreum, commonly available and consumed in the Himalayan region may have phytochemicals with potential antiviral properties against COVID-19 targets.Purpose: This study was aimed to profile the secondary metabolites of R. arboreum petals, to assess their absorption, distribution, metabolism and elimination (ADME) properties and evaluate their antiviral potential by docking against COVID-19 targets such as SARS-CoV-2 main protease (Mpro PDB ID: 6LU7) and Human Angiotensin Converting Enzyme 2 (ACE2) receptor (PDB ID: 1R4L) that mediates the viral replication and entry into the host respectively.Methods: The phytochemicals of R. arboreum petals were mainly profiled using Gas Chromatography-Mass Spectroscopy (GC-MS) and 1H-NMR. In addition, the phytochemicals reported from the literature were tabulated. The ADME properties of the phytochemicals were predicted using SwissADME tool. Molecular docking simulation of the phytochemicals against SARS-CoV-2 main protease (Mpro PDB ID: 6LU7) and Human Angiotensin converting enzyme 2 (ACE2) receptor (PDB ID: 1R4L) were carried out using PyRx.Results: R. arboreum petals were found to be rich in appreciable proportions of secondary metabolites such as Quinic acid, 3-Caffeoyl-quinic acid, 5-O-Coumaroyl-D-quinic acid, 5-O-Feruloylquinic acid, 2,4-Quinolinediamine, Coumaric acid, Caffeic acid, Epicatechin, Catechin, 3-Hydroxybenzoic acid, Shikimic acid, Protocatechuic acid, Epicatechin gallate, Quercetin, Quercetin-O-pentoside, Quercetin-O-rhamnoside, Kaempferol-O-pentoside and Kaempferol. Several of these phytochemicals were reported to exhibit inhibitory activities against a range of viruses. From the molecular docking studies, 5-O-Feruloylquinic acid, 3-Caffeoyl-quinic acid, 5-O-Coumaroyl-D-quinic acid, Epicatechin and Catechin showed strong binding affinity with SARS-CoV-2 Mpro and human ACE2 receptor.Conclusion: This report showed that R. arboreum petals are rich in several antiviral phytochemicals that also docked against SARS-CoV-2 MPro and Human ACE2 receptor. This is the first report highlighting R. arboreum petals as a reservoir of antiviral phytochemicals with potential for synergetic activities. The outcomes merit further in vitro, in vivo and clinical studies on R. arboreum phytochemicals to develop natural formulations against COVID-19 disease for therapeutic benefits.

scholarly journals Network proteins of angiotensin-converting enzyme 2 but not angiotensin-converting enzyme 2 itself are host cell receptors for SARS-Coronavirus-2 attachment

2020 ◽  
Author(s):  
Arun Kumar
Keyword(s):  
Molecular Docking ◽  
Angiotensin Converting Enzyme ◽  
Host Cell ◽  
Binding Affinity ◽  
Surface Proteins ◽  
Host Cells ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Cell Receptors ◽  
Dpp4 Inhibitors

Abstract Background: Coronaviruses causing severe acute respiratory syndrome (SARS-CoV) are known to enter the host cells by attaching to the membrane bound angiotensin-converting enzyme 2 (ACE2). Using molecular docking the efficiency of interaction between SARS-CoV-2 surface proteins and ACE2 network proteins was assessed. Materials and Methods: The ACE2 protein network was identified using the STRING database. The reported SARS-CoV-2 target proteins were searched in the protein data bank and uniport database. The protein-protein interactions were assessed by molecular docking using the Chimera software. The PubChem database was searched for known inhibitors of host cell receptors interacting with SARS-CoV-2 surface proteins. Molecular docking was performed to evaluate the binding efficacy of these compounds against the SARS-CoV-2 targets using AutoDock Vina and the docked protein-ligand complex were visualised using the Chimera and PyMOL software. Results: A low binding affinity was observed between SARS-CoV-2 spike proteins (protein S, M and 6YLA) and ACE2. Coronaviruses are also reported to bind to dipeptidyl peptidase 4 (DPP4), which is a network protein of ACE2. Network analysis showed five membrane proteins associated with ACE2. The ACE2 network proteins were assessed for their binding affinity with all known SARS-CoV-2 surface proteins. The SARS-CoV-2 surface proteins showed preferential binding to network proteins such as DPP4 and Meprin A alpha but not ACE2. The binding efficacy (affinity (-5.86 to -7.10 Kcal/mol), Ki (6.32 – 22.04 mM) and IC50 (12.63 – 113.71 mM) values) of DPP4 inhibitors (saxagliptin and sitagliptin) against SARS-CoV-2 surface proteins, was observed to be at a therapeutically feasible concentration to prevent SARS-CoV-2 attachment and entry into host cells. Conclusion: SARS-CoV-2 surface proteins has better interactions with DPP4 and Meprin A alpha host cells receptors rather than ACE2. DPP4 inhibitors (saxagliptin and sitagliptin) by binding with SARS-CoV-2 surface proteins may be helpful in preventing the virus entry into the host cells.

scholarly journals Kuwanons, Promising inhibitors against the ACE-2, main protease of SARS-CoV-2 and falcipan-2 using molecular docking

2020 ◽  
Author(s):  
Kamlesh Kumari ◽  
Durgseh Kumar ◽  
Ramappa Venkatesh Kumar ◽  
Prashant Singh
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Promising Candidate ◽  
Angiotensin Converting Enzyme 2 ◽  
Main Protease ◽  
The World ◽  
Novel Virus

Abstract In the present scenario, the COVID-19 has affected the nations throughout the world. Till date, neither a vaccine nor a potential medicine is available for the cure from SARS-CoV-2 infection. Main protease of SARS-CoV-2 is responsible for the replication and transcription. Further, this virus binds to the angiotensin converting enzyme-2 (ACE-2) so there is need to find molecule, to avoid the binding of novel virus to ACE-2. It is reported that the molecules binds to falcipan-2 can help in the reduction of infection due to SARS-CoV-2. Therefore, there is a need to find promising candidate against the receptors, spread COVID-19. In the present work, kuwanons are proposed to be promising candidates against the main protease of SARS-CoV-2, ACE-2 and falcipan-2. The interaction between the different kuwanons with different receptors has been studied using the binding energy. Kuwanon M was found to best inhibitor against the main protease of SARS-CoV-2 and ACE-2. Further, the drug-likeness properties of all the 16 kuwanons were studied. Kuwanon-M found to be best inhibitor against the ACE-2 and main protease of SARS-CoV-2 with binding energy of -165.349 and -149.952 kcal/mol respectively while kuwanon-G found out to promising against the falcipan-2 with a binding energy of -149.573 kcal/mol.

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