scholarly journals Phytoconstituents of Zingiber officinale Targeting Host viral Protein Interaction at Entry Point of SARS CoV 2 A Molecular Docking Study

2020 ◽  
Vol 5 (4) ◽  
pp. 268-277
Author(s):  
Rakesh Kumar Sharma ◽  
Ankita Singh Chakotiya
Keyword(s):  
Host Cell ◽  
Serine Protease ◽  
Zingiber Officinale ◽  
Docking Study ◽  
Critical Issue ◽  
Evidence Base ◽  
Entry Point ◽  
Spike Protein ◽  
Molecular Docking Study ◽  
Microbial Infections

Current COVID 19 outbreak is a critical issue in safeguarding public health worldwide. The lack of prophylactic drugs, vaccine and effective antiviral and other supporting therapies has prompted researchers to look for promising leads against the virus. Metabolic pathways and biochemicals involved in pathophysiology of SARS-CoV-2 can be targeted to find out effective inhibitor molecules acting at the entry point of infection. SARS-CoV-2 uses their Spike protein to dock at ACE2 and the serine protease, TMPRSS2 of host cell for Spike protein priming to get entry into the host cell. In the present study phytochemicals from Zingiber officinale were evaluated to find their binding with these proteins by conducting ligand-receptor binding docking study with AutoDockVina. The structures were observed by visualizing softwares Pymol to determine unique amino acids of receptor proteins. Physicochemical properties of phytochemicals and chemotherapeutic markers were assessed with Molinspiration tool. Docking study revealed that Gingerenone (-5.87 kcal/mol) and Zingiberene (-5.77 kcal/mol) have shown effective binding affinity towards ACE2. Shoagol (-5.72 kcal/mol), Zingerone (-5.79 kcal/mol) and Zingiberene (-5.52 kcal/mol) have shown higher binding with extracellular domain of serine protease TMPRSS2. Zingiberene scored significant binding energy of -6.23 kcal/mol with Spike protein of SARS-CoV-2. This study provides an evidence base to the experiential learning about use of Zingiber officinale in microbial infections. Once further validated, it may lead to development of herbal based anti-viral adjuvants.

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 Computational approach for the design of potential spike protein binding natural compounds in SARS- CoV2

2020 ◽  
Author(s):  
Anamika Basu ◽  
Anasua Sarkar ◽  
Ujjwal Maulik
Keyword(s):  
Natural Products ◽  
Protein Binding ◽  
Binding Site ◽  
Transmembrane Protein ◽  
Experimental Studies ◽  
Cost Effective ◽  
Docking Study ◽  
Spike Protein ◽  
Molecular Docking Study ◽  
Novel Coronavirus

Abstract Angiotensin converting enzyme 2 (ACE2) (EC:3.4.17.23) is a transmembrane protein which is considered as 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, cost effective, compared to the trial and error methods using experimental studies. Natural products are safe and easily available to treat coronavirus effected patients, in the present alarming situation. In this paper five phytochemicals which belong to flavonoid and anthraquinone subclass, selected as small molecules in molecular docking study of spike protein of SARS-CoV2 with its human receptor ACE2 molecule. From the detail analysis of their molecular binding site on spike protein binding site with its receptor, hesperidin, emodin and chrysin are selected as competent natural products from both Indian and Chinese medicinal plants, to treat COVID-19.

scholarly journals Investigation of interaction between close and open types of SARS-Cov-2 spike glycoprotein with synthesized and natural Compounds as inhibitor; Molecular Docking Study

2020 ◽  
Author(s):  
Masume Jomhori ◽  
Hamid Mosaddeghi
Keyword(s):  
Binding Site ◽  
Receptor Binding ◽  
Antiviral Drug ◽  
Severe Infection ◽  
Docking Study ◽  
Spike Protein ◽  
Spike Glycoprotein ◽  
Molecular Docking Study ◽  
Antiviral Compound ◽  
Pubchem Database

Abstract Purpose Viral diseases are increasingly endangering universal public health because of a shortage of successful antiviral therapies. The novel pandemic 2019 n-Cov2 disease (COVID-19) is recently identified as viral disorder triggered by a new type of coronavirus. This type of coronavirus binds to the host human receptors through the Spike glycoprotein(S) Receptor Binding Domain (RBD). Two types of spike protein have been identified in open and closed states in which the open type causes severe infection. Thus, this receptor is a significant target for antiviral drug design.Methods Totally 111*2 natural and synthetic compounds were chosen from the PubChem database as ligands. To recognize the ability of direct contact between ligands and the binding site of 2019 n-Cov 2 -ACE2 protein, we have docked all compounds to the protein using AutoDock Vina. The FaF3-Drugs, Pan Assay Intrusion Compounds (PAINS), absorption, distribution, metabolism, excretion (ADME) and Lipinski's rules were used to evaluate the drug-like properties of the identified ligands. Antiviral compound prediction (AVC pred) also was used to assess antivirus properties.Results The results showed that seven ligands out of all had interactions with spike protein-angiotensin converting enzyme 2 binding site. We have found that six out of seven ligands show drug-like characteristics. We also found that the fluorophenyl and propane groups of ligands had the best interaction with the binding site of the protein.Conclusion Further, our results showed the ability of these ligands to prevent receptor binding of the spike protein SARS-CoV-2, so they would be considered as novel compounds of COVID-19 therapy drugs.

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 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.

Targeting SARS-CoV-2 Spike Protein of COVID-19 with Naturally Occurring Phytochemicals: An in Silco Study for Drug Development

2020 ◽  
Author(s):  
Jitendra Subhash Rane ◽  
Aroni Chatterjee ◽  
Abhijeet Kumar ◽  
Shashikant Ray
Keyword(s):  
Receptor Binding ◽  
Docking Study ◽  
Binding Energies ◽  
Host Cells ◽  
Spike Protein ◽  
Molecular Docking Study ◽  
Angiotensin Converting Enzyme 2 ◽  
Naturally Occurring

<p>Spike glycoprotein found on the surface of SARS-CoV-2 (SARS-CoV-2S) is a class I fusion protein which helps the virus in its initial attachment with human Angiotensin converting enzyme 2 (ACE2) receptor and its consecutive fusion with the host cells. The attachment is mediated by the S1 subunit of the protein via its receptor binding domain. Upon binding with the receptor the protein changes its conformation from a pre-fusion to a post-fusion form. The membrane fusion and internalization of the virus is brought about by the S2 domain of the spike protein. From ancient times people have relied on naturally occurring substances like phytochemicals to fight against diseases and infection. Among these phytochemicals, flavonoids and non-flavonoids have been found to be the active source of different anti-microbial agents. Recently, studies have shown that these phytochemicals have essential anti-viral activities. We performed a molecular docking study using 10 potential naturally occurring flavonoids/non-flavonoids against the SARS-CoV-2 spike protein and compared their affinity with the FDA approved drug hydroxychloroquine (HCQ). Interestingly, the docking analysis suggested that C-terminal of S1 domain and S2 domain of the spike protein are important for binding with these compounds. Kamferol, curcumin, pterostilbene, and HCQ interact with the C-terminal of S1 domain with binding energies of -7.4, -7.1, -6.7 and -5.6 Kcal/mol, respectively. Fisetin, quercetin, isorhamnetin, genistein, luteolin, resveratrol<b> </b>and apigenin on the other hand, interact with the S2 domain of spike protein with the binding energies of -8.5, -8.5, -8.3, -8.2, -8.2, -7.9, -7.7 Kcal/mol, respectively. Our study suggested that, these flavonoid and non-flavonoid moieties have significantly high binding affinity for the two main important domains of the spike protein which is responsible for the attachment and internalization of the virus in the host cell and their binding affinities are much higher compared to that of HCQ. In addition, ADME (absorption, distribution, metabolism and excretion) analysis also suggested that these compounds consist of drug likeness property which may help for further explore as anti-SARS-CoV-2 agents. Further, <i>in vitro</i> and <i>in vivo</i> study of these compounds will provide a clear path for the development of novel compounds that would most likely prevent the receptor binding or internalization of the SARS-CoV-2 spike protein and therefore could be used as drugs for COVID-19 therapy. </p>

Targeting SARS-CoV-2 Spike Protein of COVID-19 with Naturally Occurring Phytochemicals: An in Silco Study for Drug Development

2020 ◽  
Author(s):  
Jitendra Subhash Rane ◽  
Aroni Chatterjee ◽  
Abhijeet Kumar ◽  
Shashikant Ray
Keyword(s):  
Receptor Binding ◽  
Docking Study ◽  
Binding Energies ◽  
Host Cells ◽  
Spike Protein ◽  
Molecular Docking Study ◽  
Angiotensin Converting Enzyme 2 ◽  
Naturally Occurring

<p>Spike glycoprotein found on the surface of SARS-CoV-2 (SARS-CoV-2S) is a class I fusion protein which helps the virus in its initial attachment with human Angiotensin converting enzyme 2 (ACE2) receptor and its consecutive fusion with the host cells. The attachment is mediated by the S1 subunit of the protein via its receptor binding domain. Upon binding with the receptor the protein changes its conformation from a pre-fusion to a post-fusion form. The membrane fusion and internalization of the virus is brought about by the S2 domain of the spike protein. From ancient times people have relied on naturally occurring substances like phytochemicals to fight against diseases and infection. Among these phytochemicals, flavonoids and non-flavonoids have been found to be the active source of different anti-microbial agents. Recently, studies have shown that these phytochemicals have essential anti-viral activities. We performed a molecular docking study using 10 potential naturally occurring flavonoids/non-flavonoids against the SARS-CoV-2 spike protein and compared their affinity with the FDA approved drug hydroxychloroquine (HCQ). Interestingly, the docking analysis suggested that C-terminal of S1 domain and S2 domain of the spike protein are important for binding with these compounds. Kamferol, curcumin, pterostilbene, and HCQ interact with the C-terminal of S1 domain with binding energies of -7.4, -7.1, -6.7 and -5.6 Kcal/mol, respectively. Fisetin, quercetin, isorhamnetin, genistein, luteolin, resveratrol<b> </b>and apigenin on the other hand, interact with the S2 domain of spike protein with the binding energies of -8.5, -8.5, -8.3, -8.2, -8.2, -7.9, -7.7 Kcal/mol, respectively. Our study suggested that, these flavonoid and non-flavonoid moieties have significantly high binding affinity for the two main important domains of the spike protein which is responsible for the attachment and internalization of the virus in the host cell and their binding affinities are much higher compared to that of HCQ. In addition, ADME (absorption, distribution, metabolism and excretion) analysis also suggested that these compounds consist of drug likeness property which may help for further explore as anti-SARS-CoV-2 agents. Further, <i>in vitro</i> and <i>in vivo</i> study of these compounds will provide a clear path for the development of novel compounds that would most likely prevent the receptor binding or internalization of the SARS-CoV-2 spike protein and therefore could be used as drugs for COVID-19 therapy. </p>

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.

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