scholarly journals In-silico Structural and Molecular Docking-Based Drug Discovery Against Viral Protein (VP35) of Marburg Virus: A potent Agent of MAVD

2021 ◽  
Author(s):  
Sameer Quazi ◽  
Javed Malik ◽  
Arnaud Martino Capuzzo ◽  
Kamal Singh Suman ◽  
Zeshan Haider
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Viral Protein ◽  
In Silico ◽  
Core Protein ◽  
Hemorrhagic Fever ◽  
Inhibitory Effect ◽  
Marburg Virus ◽  
Pubchem Database ◽  
Strong Inhibitory Effect

ABSTRACTThe Marburg virus (MARV) is a highly etiological agent of hemorrhagic fever in humans. MARV has spread across the world, including America, Australia, Europe, and different Asia countries. However, there is no approved vaccine to combat MARV, combined with a high mortality rate, which makes antiviral drugs against MARV urgent. The viral protein (VP35) is a core protein of MARV that involves multiple functions of the infection cycle. This research used an in-silico drug design technique to discover the new drug-like small molecules that inhibit VP35 replication. First, several combinations of ∼ 4260 showed that structure-based similarity above 90% was retrieved from an online “PubChem” database. Molecular docking was performed using AutoDock 4.2, and ligands were selected based on docking / S score lower than reference CID_5477931 and RMSD value between 1-2. Finally, about 50 compounds showed greater bonding producing hydrogen, Van der Waals, and polar interactions with VP35. After evaluating their binding energy strength and ADMET analysis, only CID_ 3007938 and CID_11427396 were finalized, which showed the most vital binding energy and a strong inhibitory effect with MARV’s VP35. The higher binding energy, suitable ADMET, and drug similarity parameters suggest that these “CID_ 3007938 and CID_11427396” candidates have incredible latency to inhibit MARV replication; hence, these strengths led to the treatment of MAVD.

scholarly journals In-silico Structural and Molecular Docking-Based Drug Discovery Against Viral Protein (VP40) of Marburg Virus: A Causative Agent of MAVD

2021 ◽  
Author(s):  
Sameer Quazi ◽  
Tanya Golani ◽  
Nashat Akhta ◽  
Christina Elsa Thomas ◽  
Zeshan Haider
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Viral Protein ◽  
Multiple Scales ◽  
Hemorrhagic Fever ◽  
Marburg Virus ◽  
Ligand Complex ◽  
Lipinski’S Rule ◽  
High Degree ◽  
Autodock 4.2

AbstractThe Marburg virus (MARV) is reported to induce extreme hemorrhagic fever (MHF) with a high degree of infectivity and lethality in both human and non-human primates. An appropriate vaccination for this virus’s treatment is not yet usable, and thus needs intensive attempts on multiple scales. In this study, we employed the Computer-Aided Drug Design (CADD) based approach to identify the drug-like compounds inhibiting the replication of the Viral protein (VP40) of MARV. Our database search using an online database “PubChem” retrieved ∼3000 compounds structure-based similarity. Lipinski’s rule was applied to evaluate further the drug-like compounds, followed by molecular docking-based screening, and the selection of screening ligand complex with VP40 based on S-score (lower than reference Favipiravir inhibitor) and root-mean-square-deviation (RMSD) value (probably less than 2) using AutoDock 4.2. Resultantly, ∼100 compounds were identified having strong interaction with VP40 of MARV. After evaluating their binding energy using the AutoDock 4.2 software, four compounds (CID-67534452, CID-72201087, CID-123273976, CID-153708661) were identified that showed strongest binding energy with VP40 of MARV and strong inhibition effect than the Favipiravir. Robust binding energy, useful ADMET parameters and drug-likeness suggest that these candidates “CID-67534452, CID-72201087, CID-123273976, CID-153708661” have tremendous potential to stop the replication of MARV, hence might lead to the cure of MAVD.

scholarly journals Discovery of potential drug-like compounds against Viral protein (VP40) of Marburg Virus using pharmacophoric based virtual screening from ZINC database.

2021 ◽  
Author(s):  
Sameer Quazi ◽  
Javid Ahmad Malik ◽  
Komal Singh Suman ◽  
Arnaud Martino Capuzzo ◽  
Zeshan Haider
Keyword(s):  
Binding Energy ◽  
Hemorrhagic Fever ◽  
Inhibitory Effect ◽  
Marburg Virus ◽  
Working Environment ◽  
Computer Aided Drug Design ◽  
Lipinski’S Rule ◽  
Zinc Database ◽  
Novel Drug ◽  
Selection Of

Marburg virus (MARV) has been confirmed to cause extreme hemorrhagic fever (HFM) in human and animals. The effective and suitable vaccine to treat the MARV virus is not commercialized in public and demands rigorously tested on several scales. This research used a CADD (Computer-Aided Drug Design) computational based technology to find novel drug-like compounds that could inhibit the replicating of the VP40. The pharmacophoric features bases screening was done using an online computational based software, "ZINC Pharmer". We retrieved about 32456 compounds mainly focused on the properties of pharmacophores from the ZINC database. Lipinski's rule was also used to predict these drug-like compounds. as well as molecular coupling-dependent screening and selection of VP40 screening ligand complexes based on S-rank (lower than reference) and value of root, mean square (RMSD) (bottom) to examine for reference) using the Molecular Working Environment (MOE) machine. As a result, 100 compounds were found to have a close interaction with MARV VP40, followed by the Binding energy (BE) analysis of these 100 compounds. Only 50 were the strongest binding energy than favipiravir [reference inhibitor] after using the MOE-LigX algorithm to compare their binding energy. After that, ADMET analysis predicted only five compounds (ZINC95457352, ZINC38752258, ZINC38752253, ZINC39272175, and ZINC38752377) passed the ADMET parameters and have the strongest inhibitory effect against the MARV's VP40. It has been suggested that these "drug-like" candidates have an increased ability to inhibit MARV replication, leading to treatment of MARVD.

scholarly journals MOLECULAR DOCKING TERPINEN-4-OL SEBAGAI ANTIINFLAMASI PADA ATEROSKLEROSIS SECARA IN SILICO

Jurnal Kimia ◽  
2019 ◽  
pp. 221
Author(s):  
N. M. P. Susanti ◽  
N. P. L. Laksmiani ◽  
N. K. M. Noviyanti ◽  
K. M. Arianti ◽  
I K. Duantara
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Endothelial Dysfunction ◽  
Hydrogen Bonds ◽  
In Silico ◽  
Inflammatory Process ◽  
Mapk Pathway ◽  
Chronic Inflammatory Disease ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein

Atherosclerosis is a chronic inflammatory disease that begins with endothelial dysfunction, it caused fat accumulation and plaque growth in the inner arteries walls. Endothelial dysfunction will activate the Mitogen Activated Protein Kinase (MAPK) pathway involving ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins, as well as the Nuclear Factor Kappa B (NF-kB) pathway involving IKK proteins. Terpinen-4-ol is constituent found in the bangle rhizome. The purpose of this study were to determine the affinity and mechanisms of terpinen-4-ol against ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins as anti-inflammatory in atherosclerosis performed using molecular docking method. The study was conducted exploratively with several steps such as preparation and optimization of terpinen-4-ol structure, preparation of 3D ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins, validation method of molecular docking, and docking terpinen-4-ol in these proteins. The docking result are assessed from the binding energy and hydrogen bonds formed between terpinen-4-ol and proteins. The smaller value of binding energy terpinen-4-ol with target proteins showed the complex that form more stable. The result showed that terpinen-4-ol and has activity in inhibiting the inflammatory process because it is able to disturb ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins with respective bond energy values -5,12; -5,24; -5,08; -5,88; and -4,99 Kcal/mol. The molecular mechanism in inhibiting the activity of ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins is through the formation of hydrogen bonds in these proteins. These results show that terpinen-4-ol have the potential to inhibit inflammatory process and the formation of atherosclerotic plaque can be obstructed. Keywords : atherosclerosis, terpinen-4-ol, molecular docking, in silico

scholarly journals AKTIVITAS DARI KUERSETIN SEBAGAI AGEN PENCERAH KULIT SECARA IN SILICO

Jurnal Kimia ◽  
2019 ◽  
pp. 207
Author(s):  
K. D. Adnyani ◽  
L. W. E. Lestari ◽  
H. Prabowo ◽  
P. A. I. A. Siaka ◽  
N. P. L. Laksmiani
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
In Silico ◽  
Target Protein ◽  
Related Protein ◽  
Skin Whitening ◽  
Whitening Agent ◽  
Docking Method ◽  
Tyrosinase Related Protein ◽  
Molecular Docking Method

Increasing melanogenesis process causes excessive melanin synthesis resulting in darkening of the skin color. The melanogenesis process requires mealnogenesis enzymes, one of which is tyrosinase-related protein 1. One of the flavonoid compounds that has the potential as a skin lightening agent is quercetin. The antioxidant activity of quercetin plays a very important role in antimelanogenesis. This study aims to determine the affinity and molecular mechanism of quercetin on the target protein tyrosinase-related protein 1 using in silico molecular docking method. Molecular docking is carried out through stages including optimization of the structure of quercetin compounds, preparation of the target protein tyrosinase-related protein 1, validation of the molecular docking method, and docking of quercetin on the tyrosinase-related protein 1. Docking of quercetin with tyrosinase-related protein 1 produces binding energy values of -7.81 kcal/mol, while docking of native ligand with tyrosinase-related protein 1 produces binding energy values of -5.39 kcal/mol. Quercetin has a strong affinity for tyrosinase-related protein 1 which is indicated by the binding energy from the docking results. Quercetin has activity as a skin whitening agent with in silico test with molecular mechanisms through inhibition of the activity of tyrosinase-related protein 1 enzyme.  Keywords: skin whitening agent, in silico, quercetin, tyrosinase-related protein 1

scholarly journals In-silico pharmacophore and Molecular Docking based drug discovery against Marburg Virus Viral Protein VP35; A potent of MAVD.

2021 ◽  
Author(s):  
Sameer Quazi ◽  
Shreelaxmi Gavas ◽  
Javed Ahmad Malik ◽  
Komal Singh Suman ◽  
Zeshan Haider
Keyword(s):  
Molecular Docking ◽  
Viral Protein ◽  
Virus Disease ◽  
Antiviral Drug ◽  
Computational Approach ◽  
Marburg Virus ◽  
Online Tool ◽  
Lipinski’S Rule ◽  
Zinc Database ◽  
Lipinski’S Rule Of Five

Marburg virus is a member of filoviridae and spreads severe Marburg hemorrhagic illness in humans and animals. Nowadays, there is no vaccine available that can completely stop the replication of Marburg replication. Therefore, this study is designed to repurpose the effective therapeutic antiviral drug by using a computational approach against exploring the mechanism of Marburg virus Viral protein 35. We have retrieved about 40570 drug-like small compounds from the ZINC database using the "ZINC Pharmer" online tool. Molecular docking of the ligands from the ready-to-dock database has been carried out using MOE. The five drugs have been identified to bind with VP35 possibly. A study was also performed to evaluate the drug-like characteristics of the substances for absorption, distribution, metabolism, and excretion (ADME). The findings clearly showed that ligands are interacting with the MARV VP35 protein. Interestingly, Lipinski's rule of five was observed by all ligands. These findings provide the foundation for reconstituting and utilizing molecules as a possible therapy for Marburg Virus Disease (MVD).

scholarly journals Computational Approach Revealed Potential Affinity of Antiasthmatics Against Receptor Binding Domain of 2019n-Cov Spike Glycoprotein

2020 ◽  
Author(s):  
LAMIAE ELKHATTABI ◽  
Hicham Charoute ◽  
Rachid Saile ◽  
Abdelhamid Barakat
Keyword(s):  
Molecular Docking ◽  
Receptor Binding ◽  
In Silico ◽  
Cyclic Peptide ◽  
Direct Interaction ◽  
Binding Domain ◽  
Binding Energies ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Pubchem Database

The novel COVID-19 pandemic is now a health threat, with a deep-felt impact worldwide. The new coronavirus 2019 (2019 n-Cov) binds to host human receptors through Receptor Binding Domain RBD of Spike glycoprotein (S), making it a prominent drug target. The present study aims to identify new potential hits that can inhibit the S protein using in silico approaches. Several natural and synthetics compounds (antiasthmatics, Antiviral, Antimalarial, Antibacterial, Anti-Inflammatory, cyclic peptide, and cyclic bis) were screened by molecular docking using AutoDock Vina. Additionally, we tested calcitriol and three known drugs (Azithromycin, HydroxyChloroquine, and Chloroquine ) against the spike protein to found if they have any direct interaction.<br>Our finding consists of 4 potential synthetic compounds from PubChem database, known for their antiasthmatic effects, that show highly binding energies each (-8.6 kcal/mol, 7.7kcal/mol, -7.2 kcal/mol and -7.0 kcal/mol). Another 5 natural compounds from the South African natural sources database (SANCDB) that bind to RBD of Spike with significant energy each: (Marchantin C with -7.3 kcal/mol, Riccardin C with -7.0 kcal/mol, Digitoxigenin-glucoside with -6.9 kcal/mol, D-Friedoolean-14-en-oic acid with -6.8 kcal/mol and, Spongotine A with -6.7 kcal/mol). The FaF-Drugs server was used to evaluate the drug-like properties of the identified compounds. Additionally, Calcitriol, Azithromycin, and HydroxyChloroquine have an appreciable binding affinity to 2019-nCoV S, suggesting a possible mechanism of action. Using in silico approaches like molecular docking and pharmacokinetic properties, we showed new potential inhibitors. Our findings need further analysis, and chemical design for more effective derivatives of these compounds speculated to disrupt the viral recognition of host receptors.

scholarly journals Computational Molecular Docking and Virtual Screening Revealed Promising SARS-CoV-2 Drugs

2020 ◽  
Author(s):  
Maryam Hosseini ◽  
Wanqiu Chen ◽  
Charles Wang
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Virtual Screening ◽  
Clinical Studies ◽  
Inhibitory Effect ◽  
Docking Approach ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Potential Inhibitors ◽  
Computational Molecular Docking

The pandemic of novel coronavirus disease 2019 (COVID-19) is rampaging the world with more than 1.4 million of confirmed cases and more than 85,000 of deaths across world by April 9th, 2020. There is an urgent need to identify effective drugs to fight against the virus. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the family of coronaviruses consisting of four structural and 16 non-structured proteins. Three non-structural proteins such as main protease, papain like protease, and RNA-dependent RNA polymerase are believed to play a crucial role in the virus replication. We applied a computational ligand-receptor binding modeling and performed a comprehensive virtual screening on the FDA-approved drugs against these three SARS-CoV-2 proteins using AutoDock Vina. Our computational studies indicated that Simeprevir, Ledipasvir, Idarubicin, Saquinavir, Ledipasivir, Partitaprevir, Glecaprevir, and Velpatasvir are all promising inhibitors, which displayed a lower binding energy (higher inhibitory effect) than Remdesivir, Lopinavir, and Ritonavir. However, we found that chloroquine and hydroxychloroquine, which showed efficacy in treating the COVID-19 in recent clinical studies, had high binding energy with all three proteins, suggesting they may work through a different mechanism. We also identified several novel drugs as potential inhibitors against SARS-CoV-2, including antiviral Raltegravir; antidiabetic Amaryl; antibiotics Retapamulin, Rifimixin, and Rifabutin; antiemetic Fosaprepitant and Netupitant. In summary, our computational molecular docking approach and virtual screening identified some promising candidate SARS-CoV-2 drugs that may be considered for further clinical studies.

The Inhibitory Effect of Three Essential Oils on Candida rugosa Lipase: In Vitro and In Silico Studies

2020 ◽  
Vol 10 (3) ◽  
pp. 208-215 ◽  
Author(s):  
Talia Serseg ◽  
Khedidja Benarous ◽  
Mohamed Yousfi
Keyword(s):  
Molecular Docking ◽  
Essential Oils ◽  
In Silico ◽  
Candida Rugosa ◽  
Inhibitory Effect ◽  
Mentha Piperita ◽  
Inhibition Mechanism ◽  
Syzygium Aromaticum ◽  
In Silico Studies

Background: Essential oils have been used for centuries. EOs are gaining increasing interest because of their acceptance by consumers and their safe status. For the first time, the effect of essential oils on the inhibition of lipases has been investigated in this work. Objective: We aimed in this study to investigate in vitro the inhibitory effects of the three essential oils of most used spices: Peppermint (Mentha piperita L.), cinnamon (Cinnamomum zeylanicum L.) and Cloves (Syzygium aromaticum L. Merr. et Perry) against Candida rugose lipase. In silico studies using molecular docking have been achieved to study the inhibition mechanism of major compounds of EO: menthol, carvacrol, eugenol and cinnamylaldehyde toward CRL. Methods: The inhibitory effect of three essential oils were determined by candida rugosa enzyme and pNP-L as substrate using spectrophotometry. Autodock vina was used for molecular docking with 50 runs. Results: We have found that these essential oils have a strong inhibitory effect with IC50 values 1.09, 1.78 and 1.13 mg/ml compared with Orlistat 0.06 mg/ml. The results show competitive inhibition for the three major compounds Menthol, Carvacrol and Eugenol with uncompetitive inhibition for Cinnamaldehyde. Different repetition ratios of hydrogen bonds and hydrophobic interactions were observed. The saved interactions were with His449, Ser209, Gly123, Gly124 and Phe344 for all molecules. Conclusion: These observations support using and considering essential oils and their major compounds as good sources for design new drugs to treat candidiasis and other diseases related to Lipases.

Pharmacological study of A3 Adenosine receptor agonist (AB Meca) in xenograft lung cancer model in mice through in silico and in vivo approach: Targeting TNF-α

2021 ◽  
Vol 18 ◽  
Author(s):  
Nilay Solanki ◽  
Leena Patel ◽  
Shaini Shah ◽  
Ashish Patel ◽  
Swayamprakash Patel ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Binding Energy ◽  
Adenosine Receptor ◽  
In Silico ◽  
Human Lung Cancer ◽  
A3ar Agonist ◽  
Adenosine Receptor Agonist ◽  
Tnf Α

Background: Lung cancer is the leading cause of mortality in India. Adenosine receptor (AR) has emerged as a novel cancer-specific target. A3AR levels are upregulated in various tumor cells, which may mean that the specific AR may act as a biological marker and target specific ligands leading to cell growth inhibition. Aim: Our aim was to study the utility of the TNF-α agonist, AB MECA, by in silico (molecular docking) and in vitro (human cancer cells in xenografted mice) studies. Method: Molecular docking on the AB-meca and TNF-α was performed using AutoDock. A549 Human lung cancer 2 ×106 cells per microliter per mouse injected via intrabronchial route. Rat TNF-α level was assessed by ELISA method. Results: AB Meca's predicted binding energy (beng) with TNF-α was 97.13 kcal/mol, and the compatible docking result of a small molecular inhibitor with TNF-α native ligand beng was 85.76 kcal/mol. In vivo, a single dose of lung cancer cell A549 is being researched to potentiate tumor development. Doxorubicin and A3AR agonist therapies have lowered TNF-alpha levels that were associated with in silico function. The A3AR Agonist myeloprotective effect was also found in groups treated with doxorubicin. Conclusion: AB MECA’s higher binding energy (beng) with TNF-α mediated reduction of tumor growth in our lung cancer in vivo model suggests that it may be an effective therapy for lung cancer.

scholarly journals AKTIVITAS ANTI-RHEUMATOID ARTHRITIS DARI BRAZILIN DAN BRAZILEIN SECARA IN SILICO

Jurnal Kimia ◽  
2019 ◽  
pp. 153
Author(s):  
G. A. K. Amarawati ◽  
N. M. P. Susanti ◽  
N. P. L. Laksmiani
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Docking ◽  
Binding Energy ◽  
In Silico ◽  
Inflammatory Process ◽  
Joint Destruction ◽  
Protein Preparation ◽  
3D Structures ◽  
Docking Method ◽  
Molecular Docking Method

Rheumatoid arthritis is an autoimmune disease that occur by inflammation chronic which persist as a permanent symptom. That inflammatory process caused joint destruction. Production of pro-inflammatory sytokin such as Tumor Necrosis Factor Alpha (TNF-?) stimulate an autoimmunity. Active TNF-? plays a role in the occurrence of chronic inflammation, in which the formation of active TNF-? is regulated by TNF-? Converting Enzyme (TACE). Brazilin and brazilein are known to have anti-inflammatory activity and immunommodulator potentially as anti-rheumatoid arthritis. The purpose of this study were to determine the affinity and mechanisms of brazilin and brazilein against TACE proteins as anti-rheumatoid arthritis perfomed using molecular docking method. The study was conducted exploratively with several steps such as databases preparation of 3D structures brazilin, brazilein, TACE protein, optimization of brazilin and brazilein 3D structures, protein preparation, molecular docking method validation, and docking brazilin and brazilein in these proteins. The docking results are assessed from the binding energy and hydrogen bonds formed between brazilin and brazilein in proteins. The smaller value to the binding energy, will made the bond between brazilin and brazilein with proteins will be stronger and more stable. The results showed that brazilin and brazilein have activities as anti-rheumatoid arthritis because they are able to inhibit TACE proteins with respective bond energy values -7,24 for brazilin and – 7,59 kcal/mol for brazilein. These results show that brazilin and brazilein have the potential to inhibit inflammatory process and joint destruction in rheumatoid arthritis. Keywords : brazilin, brazilein, in silico, rheumatoid arthritis

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