scholarly journals Epigallocatechin gallate and theaflavin gallate interaction in SARS‐CoV ‐2 spike‐protein central channel with reference to the hydroxychloroquine interaction: Bioinformatics and molecular docking study

2020 ◽  
Author(s):  
Smarajit Maiti ◽  
Amrita Banerjee
Keyword(s):  
Molecular Docking ◽  
Epigallocatechin Gallate ◽  
Docking Study ◽  
Spike Protein ◽  
Central Channel ◽  
Molecular Docking Study

scholarly journals Epigallocatechin-Gallate and Theaflavin-Gallate Interaction in SARS CoV-2 Spike-Protein Central-Channel with Reference to the Hydroxychloroquine Interaction: Bioinformatics and Molecular Docking Study

2020 ◽  
Author(s):  
Smarajit Maiti ◽  
Amrita Banerjee
Keyword(s):  
Molecular Docking ◽  
Epigallocatechin Gallate ◽  
Docking Study ◽  
Host Cells ◽  
Spike Protein ◽  
Health Economy ◽  
Central Channel ◽  
Molecular Docking Study ◽  
Drug Induced ◽  
Protein Nucleic Acid

SARS CoV-2 or COVID-19 pandemic global-outbreak created the most unstable situation of human health-economy. Last two decades different parts of the word experienced smaller or bigger outbreak related to human-coronaviruses. The spike-glycoproteins of the COVID-19 (similar to SARS-CoV) attach to the angiotensin-converting-enzyme (ACE-2) and transit over a stabilized open-state for the viral-internalization to the host-cells and propagate with great efficacy. Higher rate of mutability makes this virus unpredictable/less-sensitive to the protein/nucleic-acid based-drugs. In this emergent situation, drug-induced destabilization of spike-binding to RBD could be a good strategy. In the current study we demonstrated by Bioinformatics (CASTp: Computed-Atlas-of-Surface-Topography, PyMol: molecular-visualization) and Molecular docking (PatchDock) experiments that tea flavonoids catechin-products mainly EGCG or other like theaflavin gallate demonstrated higher Atomic Contact Energy (ACE), surface area and more amino-acid interactions than hydroxychloroquine (HCQ) during binding in the central channel of the spike-protein. Moreover, out of three distinct binding-sites (I, II and III) of spike core when HCQ binds only with site III (farthest from the vCoV-RBD of ACE2 contact), EGCG and TG bind all three sites. As because site I and II is in closer contact with open state location and viral-host contact area so these drugs might have significant effects. Taking into account the toxicity/side-effects by CQ/HCQ, present drugs may be important. Our laboratory is working on tea flavonoids and other phytochemicals in the protection from toxicity, DNA/mitochondrial damage, inflammation etc. The present data might be helpful for further analysis of flavonoids in this emergent pandemic situation.

scholarly journals Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (Mpro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study

2020 ◽  
Author(s):  
Trina Ekawati Tallei ◽  
Sefren Geiner Tumilaar ◽  
Nurdjannah Jane Niode ◽  
Fatimawali Fatimawali ◽  
Billy Johnson Kepel ◽  
...  
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Bioactive Compounds ◽  
Binding Free Energy ◽  
Epigallocatechin Gallate ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Ligand Complex ◽  
Main Protease ◽  
Glycoprotein Inhibitors

Since the outbreak of the COVID-19 (Coronavirus Disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit the Main Protease (Mpro) and Spike (S) glycoprotein of SARS-CoV-2. The evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. A rule of five (RO5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. The determination of the docking score was done by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs' free energy of binding / ΔG). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. The results showed that hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine, and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and nabiximols had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as Mpro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine, and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19. As judged by the RO5 and previous study by others, the compounds kaempferol, herbacetin, eugenol, and 6-shogaol have good oral bioavailability, so they are also seen as promising candidates for the development lead compounds to treat infections caused by SARS-CoV-2.

scholarly journals Development of SARS-CoV-2 Inhibitors Using Molecular Docking Study with Different Coronavirus Spike Protein and ACE2

2021 ◽  
Vol 1 (1) ◽  
pp. 1-14
Author(s):  
Israa Mohamed Shamkh ◽  
Dina Pratiwi
Keyword(s):  
Molecular Docking ◽  
Host Cell ◽  
Binding Free Energy ◽  
Hydroxypropyl Methylcellulose ◽  
Docking Study ◽  
Cell Receptor ◽  
Spike Protein ◽  
Molecular Docking Study ◽  
Binding Ability ◽  
S Protein

The novel coronavirus SARS-CoV-2 is an acute respiratory tract infection that emerged in Wuhan city, China. The spike protein of coronaviruses is the main driving force for host cell recognition and is responsible for binding to the ACE2 receptor on the host cell and mediates the fusion of host and viral membranes. Recognizing compounds that could form a complex with the spike protein (S-protein) potently could inhibit SARS-CoV-2 infections. The software was used to survey 300 plant natural compounds or derivatives for their binding ability with the SARS-CoV-2 S-protein. The docking score for ligands towards each protein was calculated to estimate the binding free energy. Four compounds showed a strong ability to bind with the S-protein (neohesperidin, quercetin 3-O-rutinoside-7-O-glucoside, 14-ketostypodiol diacetate, and hydroxypropyl methylcellulose) and used to predict its docking model and binding regions. The highest predicted ligand/protein affinity was with quercetin 3-O-rutinoside-7-O-glucoside followed by neohesperidin. The four compounds were also tested against other related coronavirus and showed their binding ability to S-protein of the bat, SARS, and MERS coronavirus strains, indicating that they could bind and block the spike activities and subsequently prevent them infection of different coronaviruses. Molecular docking also showed the probability of the four ligands binding to the host cell receptor ACE2. The interaction residues and the binding energy for the complexes were identified. The strong binding ability of the four compounds to the S-protein and the ACE2 protein indicates that they might be used to develop therapeutics specific against SARS-CoV-2 and close related human coronaviruses.

scholarly journals In Silico Docking for Inhibition Neuropilin-1 (SARS-CoV-2 receptor) by Some Natural and Approved Drugs

2020 ◽  
Author(s):  
mohamed seadawy ◽  
Mohamed Shamel ◽  
Aya Ahmed ◽  
Abdel Rahman N. Zekri
Keyword(s):  
Natural Products ◽  
Molecular Docking ◽  
Severe Acute Respiratory Syndrome ◽  
Docking Study ◽  
Spike Protein ◽  
Molecular Docking Study ◽  
In Silico Docking ◽  
Neuropilin 1 ◽  
Approved Drugs

Abstract Background: Neuropilin-1 (NRP-1) is a multifunctional transmembrane receptor for ligands that affect developmental axonal growth and angiogenesis. Beside its role in cancer, NRP-1 is a reported entrance for several viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19). Methods: We made Insilco docking between the spike protein and Neuropilin-1 using Cluspro 2.0 software. Therefore, Neuropilin-1 becomes host factor for SARS-CoV-2 infection. Then by using molecular docking, we test nine compounds against Neuropilin-1 for its inhibition. Results: Our result revealed that NRP-1 receptor is considered as Therapeutic target for SARS-CoV2 treatment and screened with natural compounds and drugs (e.g. Carvacrol, Thymol, Amantadine, Daclatasvir, Ravidasvir, Remdesivir, Sofosbuvir, Hesperidine and Thymoquinone) by molecular docking study. Conclusion: These natural products and drugs may emerge as potential Neuropilin-1 inhibitor. However, additional exploration is predictable for the investigation of the essential use of the drugs and herbs containing these natural products and their in-vivo activity.

scholarly journals Molecular docking study of potential phytochemicals and their effects on the complex of SARS-CoV2 spike protein and human ACE2

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Anamika Basu ◽  
Anasua Sarkar ◽  
Ujjwal Maulik
Keyword(s):  
Natural Products ◽  
Molecular Docking ◽  
Antiviral Activity ◽  
Binding Sites ◽  
Transmembrane Protein ◽  
Experimental Studies ◽  
Docking Study ◽  
Spike Protein ◽  
Dimensional Structure ◽  
Molecular Docking Study

Abstract Angiotensin converting enzyme 2 (ACE2) (EC:3.4.17.23) is a transmembrane protein which is considered as a receptor for spike protein binding of novel coronavirus (SARS-CoV2). Since no specific medication is available to treat COVID-19, designing of new drug is important and essential. In this regard, in silico method plays an important role, as it is rapid and cost effective compared to the trial and error methods using experimental studies. Natural products are safe and easily available to treat coronavirus affected patients, in the present alarming situation. In this paper five phytochemicals, which belong to flavonoid and anthraquinone subclass, have been selected as small molecules in molecular docking study of spike protein of SARS-CoV2 with its human receptor ACE2 molecule. Their molecular binding sites on spike protein bound structure with its receptor have been analyzed. From this analysis, hesperidin, emodin and chrysin are selected as competent natural products from both Indian and Chinese medicinal plants, to treat COVID-19. Among them, the phytochemical hesperidin can bind with ACE2 protein and bound structure of ACE2 protein and spike protein of SARS-CoV2 noncompetitively. The binding sites of ACE2 protein for spike protein and hesperidin, are located in different parts of ACE2 protein. Ligand spike protein causes conformational change in three-dimensional structure of protein ACE2, which is confirmed by molecular docking and molecular dynamics studies. This compound modulates the binding energy of bound structure of ACE2 and spike protein. This result indicates that due to presence of hesperidin, the bound structure of ACE2 and spike protein fragment becomes unstable. As a result, this natural product can impart antiviral activity in SARS CoV2 infection. The antiviral activity of these five natural compounds are further experimentally validated with QSAR study.

scholarly journals Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (Mpro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study

2020 ◽  
Author(s):  
Trina Ekawati Tallei ◽  
Sefren Geiner Tumilaar ◽  
Nurdjannah Jane Niode ◽  
Fatimawali Fatimawali ◽  
Billy Johnson Kepel ◽  
...  
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Bioactive Compounds ◽  
Binding Free Energy ◽  
Biological Activities ◽  
Epigallocatechin Gallate ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Glycoprotein Inhibitors

Background: Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the cause of COVID-19. The search for plant-based antivirals against the SARS-CoV-2 is promising, as several plants have been shown to possess antiviral activities against betacoronaviruses (beta-CoVs) Objective: The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit Main Protease (Mpro) (PDB code: 6LU7) and Spike (S) Glycoprotein (PDB code: 6VXX) of SARS-CoV-2. Methods: Evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. For each compound that was docked, a rule of five was calculated to determine whether a compound with certain pharmacological or biological activities might have chemical and physical properties that would make it an active drug orally in humans. Determination of the docking score was done by selecting the conformation of the ligand that has the lowest binding free energy (best pose). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. Results: The results showed that hesperidine, cannabinoids, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and cannabinoids had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as Mpro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Conclusion: Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19.

scholarly journals Metal-Bound Methisazone; Novel Drugs Targeting Prophylaxis and Treatment of SARS-CoV-2, a Molecular Docking Study

2021 ◽  
Vol 22 (6) ◽  
pp. 2977
Author(s):  
Ahmed Abdelaal Ahmed Mahmoud M. Alkhatip ◽  
Michail Georgakis ◽  
Lucio R. Montero Valenzuela ◽  
Mohamed Hamza ◽  
Ehab Farag ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Study ◽  
Docking Studies ◽  
Binding Energies ◽  
Spike Protein ◽  
Molecular Docking Study ◽  
In Silico Docking ◽  
Main Protease ◽  
Binding Pockets

SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at −8.3 kcal/mol, followed by Zn and Ca at −8.0 kcal/mol, and Fe and Mg at −7.9 kcal/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be singly or multiply occupied on all proteins tested. The best binding energy was with Mn–Methisazone versus spike protein, and the largest cumulative increases in binding energies were found with PlPr. We suggest that further studies are warranted to identify whether these compounds may be effective for treatment and/or prophylaxis.

scholarly journals A Potential Inhibition Process of Ricin Protein with the flavonoids Quercetin and Epigallocatechin Gallate. A Quantum-Chemical and Molecular Docking Study

Processes ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 1393
Author(s):  
Mayra Cristina Martínez-Ceniceros ◽  
Linda-Lucila Landeros-Martínez ◽  
Nora-Aydeé Sánchez-Bojorge ◽  
Fabiola Sandoval-Salas ◽  
Hilda Amelia Piñón-Castillo ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Quantum Chemical ◽  
Ricinus Communis ◽  
Epigallocatechin Gallate ◽  
Docking Study ◽  
Binding Energies ◽  
Molecular Structures ◽  
Molecular Docking Study ◽  
Inhibition Process

Castor bean (Ricinus Communis) oil has been reported as one of the most important bio-based fuels; however, high amounts of toxic solid residue are generated in the production. This toxicity is due to several molecules, ricin protein being the most studied compound. The inhibition of the ricin protein is essential for eliminating its toxicity. The objective of this study is to predict the possible inhibition process via the interactions between the ricin protein and the flavonoids quercetin (Q) and epigallocatechin gallate (EGCG). The molecular structures of the complexes formed between the ricin protein and flavonoids were studied using quantum-chemical and molecular docking calculations to analyze the type of interaction, active site of the protein, binding energies, and different conformations in the inhibition process. Different methodologies were applied for the molecular structure determination; the best approximation was obtained with B3LYP/6-31G (d,p) theoretical methodology. Mappings of electrostatic potential (MEP) and frontier molecular orbitals were used for the identification of the probable sites of interaction, which were confirmed by molecular docking. The adjustment and alignment of flavonoid groups before and after the interaction, and charge transfer parameters, showed that Q and EGCG act as electron donors inside of the active site in ricin.

scholarly journals Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (Mpro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study

2020 ◽  
Author(s):  
Trina Ekawati Tallei ◽  
Sefren Geiner Tumilaar ◽  
Nurdjannah Jane Niode ◽  
Fatimawali Fatimawali ◽  
Billy Johnson Kepel ◽  
...  
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Bioactive Compounds ◽  
Binding Free Energy ◽  
Biological Activities ◽  
Epigallocatechin Gallate ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Glycoprotein Inhibitors

Background: Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the cause of COVID-19. The search for plant-based antivirals against the SARS-CoV-2 is promising, as several plants have been shown to possess antiviral activities against betacoronaviruses (beta-CoVs) Objective: The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit Main Protease (Mpro) (PDB code: 6LU7) and Spike (S) Glycoprotein (PDB code: 6VXX) of SARS-CoV-2. Methods: Evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. For each compound that was docked, a rule of five was calculated to determine whether a compound with certain pharmacological or biological activities might have chemical and physical properties that would make it an active drug orally in humans. Determination of the docking score was done by selecting the conformation of the ligand that has the lowest binding free energy (best pose). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. Results: The results showed that hesperidine, cannabinoids, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and cannabinoids had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as Mpro/3CLpro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Conclusion: Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19.

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