scholarly journals Molecular dynamics analysis of phytochemicals from Ageratina adenophora against COVID-19 main protease (Mpro) and human angiotensin-converting enzyme 2 (ACE2)

2021 ◽  
Vol 32 ◽  
pp. 101924
Author(s):  
Netra Prasad Neupane ◽  
Abhishek Kumar Karn ◽  
Imdad Husen Mukeri ◽  
Prateek Pathak ◽  
Praveen Kumar ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Angiotensin Converting Enzyme ◽  
Dynamics Analysis ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Main Protease ◽  
Ageratina Adenophora

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 Computational analysis on the ACE2-derived peptides for neutralizing the ACE2 binding to the spike protein of SARS-CoV-2

2020 ◽  
Author(s):  
Cecylia S. Lupala ◽  
Vikash Kumar ◽  
Xuanxuan Li ◽  
Xiao-dong Su ◽  
Haiguang Liu
Keyword(s):  
Molecular Dynamics ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Computational Analysis ◽  
Spike Protein ◽  
Short Peptides ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Dynamics Simulations

ABSTRACTThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19, is spreading globally and has infected more than 3 million people. It has been discovered that SARS-CoV-2 initiates the entry into cells by binding to human angiotensin-converting enzyme 2 (hACE2) through the receptor binding domain (RBD) of its spike glycoprotein. Hence, drugs that can interfere the SARS-CoV-2-RBD binding to hACE2 potentially can inhibit SARS-CoV-2 from entering human cells. Here, based on the N-terminal helix α1 of human ACE2, we designed nine short peptides that have potential to inhibit SARS-CoV-2 binding. Molecular dynamics simulations of peptides in the their free and SARS-CoV-2 RBD-bound forms allow us to identify fragments that are stable in water and have strong binding affinity to the SARS-CoV-2 spike proteins. The important interactions between peptides and RBD are highlighted to provide guidance for the design of peptidomimetics against the SARS-CoV-2.

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 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 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.

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