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 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 Molecular Docking Studies of Flavonoids from Andrographis paniculata as Potential Acetylcholinesterase, Butyrylcholinesterase and Monoamine Oxidase Inhibitors Towards the Treatment of Neurodegenerative Diseases

2020 ◽  
Vol 11 (3) ◽  
pp. 9871-9879
Keyword(s):  
Molecular Docking ◽  
Monoamine Oxidase ◽  
Neurodegenerative Diseases ◽  
Docking Studies ◽  
Monoamine Oxidase Inhibitors ◽  
Andrographis Paniculata ◽  
Lipinski’S Rule ◽  
Bioinformatic Tools ◽  
Pubchem Database ◽  
Lipinski’S Rule Of Five

Neurodegenerative diseases have been characterized by loss of neuron structures as well as their functions. This study was designed to assess molecular docking of flavonoids from Andrographis paniculata as potential acetylcholinesterase, butyrylcholinesterase, and monoamine oxidase inhibitors in the treatment of neurodegenerative diseases. Eight identified possible inhibitors of acetylcholinesterase, butyrylcholinesterase, and monoamine oxidase from Andrographis paniculata were retrieved from the PubChem database. The molecular docking, ADMET, and Lipinski’s rule of five were examined using different bioinformatic tools. It was shown that only rutin has the highest binding affinity (-12.6 kcal/mol) than the standard used. ADMET results demonstrated that all the eight compounds are druggable candidates except rutin. Also, only tangeritin has a blood-brain barrier (BBB) permeation potential. Hence, it can be deduced that all flavonoid compounds from Andrographis paniculata are orally druggable, which can make them useful in the treatment of neurodegenerative diseases better than donepezil.

In Silico Discovery of Novel Inhibitors Against Main Protease (Mpro) of SARS-CoV-2 Using Pharmacophore and Molecular Docking Based Virtual Screening from ZINC Database

2020 ◽  
Author(s):  
Zeshan Haider ◽  
Muhammad Muneeb Subhani ◽  
Muhammad Ansar Farooq ◽  
Maryum Ishaq ◽  
Maryam Khalid ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Effective Vaccine ◽  
Ligand Complex ◽  
Online Tool ◽  
Public Health Emergencies ◽  
Main Protease ◽  
Zinc Database ◽  
Recent Outbreak ◽  
Selection Of

Recent outbreak of Coronavirus Disease 2019 (COVID-19) caused by a novel ‘SARS-CoV-2’ virus resulted public health emergencies across the world. An effective vaccine to cure this virus is not yet available, thus requires concerted efforts at various scales. In this study, we employed Computer Aided Drug Design (CADD) based approach to identify the drug-like compounds - inhibiting the replication of main protease (Mpro) of SARS-CoV-2. Our database search using online tool “ZINC pharmer” retrieved ~1500 compounds based on pharmacophore features. Lipinski’s rule was applied to further evaluate the drug-like compounds, followed by molecular docking-based screening, and the selection of screening ligand complex with Mpro based on S-score (higher than reference inhibitor) and root-mean-square deviation (RMSD) value (less than reference inhibitor) using Molecular Operating Environment (MOE) system. Resultantly, ~200 compounds were identified having strong interaction with Mpro of SARS-CoV-2. After evaluating their binding energy using the MOE LigX algorithm, three compounds (ZINC20291569, ZINC90403206, ZINC95480156) were identified that showed highest binding energy with Mpro of SARS-CoV-2 and strong inhibition effect than the reference inhibitor. It is suggested that these candidate “drug-like compounds” have greater potential to stop the replication of SARS-CoV-2, hence might lead to the cure of COVID-19.

scholarly journals Ligand Based 3D-QSAR Pharmacophore, Molecular Docking and Adme to Identify Potential Fibroblast Growth Factor Receptor 1 Inhibitors 

2020 ◽  
Author(s):  
Zizhong Tang ◽  
Lu Huang ◽  
Xiaoli Fu ◽  
Haoxiang Wang ◽  
Biao Tang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Growth Factor Receptor ◽  
Pharmacophore Model ◽  
3D Qsar ◽  
Drug Carriers ◽  
Therapeutic Effects ◽  
Lipinski’S Rule ◽  
Discovery Studio ◽  
Zinc Database

Abstract The FGF/FGFR system may affect tumor cells and stromal microenvironment through autocrine and paracrine stimulation, thereby significantly promoting oncogene transformation and tumor growth. Abnormal expression of FGFR1 in cells is considered to be the main cause of tumorigenesis and a potential target for the treatment of cancer. In this study, a combination of structure-based drug carriers and molecular docking-based virtual screening was used to screen new potential FGFR1 inhibitors. Twenty-one known inhibitors were collected as training sets to establish a 3D-QSAR pharmacophore model, and cost analysis, test set validation, and Fischer randomization test were used to validate the efficiency of the pharmacophore model. In Accelrys Discovery Studio 2016, the zinc database was filtered by Lipinski's Rule of Five and SMART's filtration. Then, Hypo01 was used for virtual screening of ZINC database. Compounds with predicted activity values less than 1 μM were molecularly docked with FGFR1 protein crystals, the docking results were observed, and the interaction between compounds and targets was studied. The absorption, distribution, metabolism and excretion (ADME) and toxicity of potential inhibitors were studied, and a compound with new structural scaffolds were obtained. It could be further studied to explore their better therapeutic effects.

scholarly journals PENENTUAN SENYAWA POTENSIAL DARI BUAH SEMANGKA (Citrullus Lanatus) SEBAGAI KANDIDAT OBAT DISLIPIDEMIA

2019 ◽  
Vol 10 (1) ◽  
pp. 42
Author(s):  
Muhammad Fauzi ◽  
Effan Cahyati Junaedi ◽  
Agus Rusdin
Keyword(s):  
Molecular Docking ◽  
Citrullus Lanatus ◽  
Lipinski’S Rule ◽  
Protein Target ◽  
Lipinski’S Rule Of Five

Dislipedemia merupakan penyakit yang disebabkan oleh abnormalitas pada metabolisme lipid. Sampai saat ini simvastatin masih menjadi lini pertama dalam pengobatan dislipidemia. Namun selain mengggunakan obat sintetis, bahan alam juga dapat dimanfaatkan dalam mengatasi kolesterol tinggi sebagai alternatif menurunkan kadar kolesterol. Salah satunya adalah buah semangka (Citrullus lanatus) yang mengandung senyawa arginine, betain, sitrulin, kukurbitasin, likopen dan pekin. Penelitian ini dilakukan dengan menggunakan metode penambatan molekuler (molecular docking) yang digunakan untuk menyeleksi senyawa berdasarkan interaksinya dengan protein target dan prediksi biovaibilitasnya.. Tujuan penelitian ini adalah mencari potensi senyawa dari buah semangka untuk dijadikan kandidat obat dislipidemia. Molecular docking terhadap simvastatin sebagai obat pembanding memberikan energi bebas sebesar -9.05 kkal/mol dengan asam amino yang terikat adalah LYS692, ALA751, LYS735, ARG590, SER684, LYS691, ASN755. Serin (SER684) merupakan asam amino kunci dan sering memainkan peran penting dalam katalisator enzim. Hasil pengujian terhadap 6 senyawa yang terkandung didalam buah semangka, terdapat dua senyawa potensial yaitu sitrulin dan pektin. Senyawa sitrulin memberikan energi bebas -5.67 kkal/mol dengan asam amino yang terikat adalah GLU559, ARG590, LYS735, SER684, LYS692, ASP690. Senyawa pektin memberikan energi bebas -7.27 kkal/mol dengan asam amino yang terikat adalah ARG590, SER684, LYS692, ASP690, LYS691. Artinya senyawa tersebut mampu menghambat biosintesis kolesterol. Penentuan prediksi sifat biovaibilitas menunjukkan semua senyawa memenuhi parameter Lipinski’s rule of five sehingga kedua senyawa tersebut berpotensi sebagai kandidat obat dislipidemia. Kata kunci: Buah Semangka, Dislipidemia, Molecular Docking

scholarly journals Novel Coronavirus (SARS-CoV-2) Main Protease: Molecular docking of Puerarin as a Potential inhibitor

2020 ◽  
Author(s):  
Oluwafemi Adeleke Ojo ◽  
Adebola Busola Ojo ◽  
Odunayo Anthonia Taiwo ◽  
Olarewaju M Oluba
Keyword(s):  
Molecular Docking ◽  
Rna Virus ◽  
Drug Candidate ◽  
Lipinski’S Rule ◽  
Global Pandemic ◽  
Main Protease ◽  
Lipinski’S Rule Of Five ◽  
Novel Coronavirus ◽  
Research World ◽  
High Binding Affinity

Abstract SARS-CoV-2 a single stranded RNA virus which triggered the global pandemic Coronavirus Disease- 2019 (COVID-2019). It has infected about 2,844,712 patients and brought forth mortality rate to about 201,315 among 216 countries as cited by WHO. Drugs including Chloroquine and Hydroxychloroquine derivatives are being administered in most urgent cases; although, with probable side effects to people with metabolic disorders. Thus, unavailability of authorized drugs and treatment for this pandemic demands the research world to discover natural compounds with potency to cure it. This paper assesses the isoflavonoid puerarin from Pueraria lobata as a possible inhibitor of the main protease of SARS-COV-2 (Mpro) via in silico approach, for example molecular docking, Lipinski’s rule of five and toxicity prediction (ADME). Puerarin revealed high binding affinity with the target site of SARS-CoV-2 main protease. This compound slightly meets the criteria of Lipinski’s rule and does not possess properties that could cause adverse effects in humans thus, making puerarin a potential drug candidate to investigate for its usage against COVID-19.

scholarly journals Molecular Docking and Molecular Dynamics Aided Virtual Search of OliveNet™ Directory for Secoiridoids to Combat SARS-CoV-2 Infection and Associated Hyperinflammatory Responses

2021 ◽  
Vol 7 ◽  
Author(s):  
Neelaveni Thangavel ◽  
Mohammad Al Bratty ◽  
Hassan Ahmad Al Hazmi ◽  
Asim Najmi ◽  
Reem Othman Ali Alaqi
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Oral Absorption ◽  
Olive Tree ◽  
Viral Disease ◽  
S Protein ◽  
Lipinski’S Rule ◽  
Main Protease ◽  
Lipinski’S Rule Of Five ◽  
The Moment

Molecular docking and molecular dynamics aided virtual search of OliveNet™ directory identified potential secoiridoids that combat SARS-CoV-2 entry, replication, and associated hyperinflammatory responses. OliveNet™ is an active directory of phytochemicals obtained from different parts of the olive tree, Olea europaea (Oleaceae). Olive oil, olive fruits containing phenolics, known for their health benefits, are indispensable in the Mediterranean and Arabian diets. Secoiridoids is the largest group of olive phenols and is exclusive to the olive fruits. Functional food like olive fruits could help prevent and alleviate viral disease at an affordable cost. A systematized virtual search of 932 conformers of 78 secoiridoids utilizing Autodock Vina, followed by precision docking using Idock and Smina indicated that Nüzhenide oleoside (NZO), Oleuropein dimer (OED), and Dihydro oleuropein (DHO) blocked the SARS-CoV-2 spike (S) protein-ACE-2 interface; Demethyloleuropein (DMO), Neo-nüzhenide (NNZ), and Nüzhenide (NZE) blocked the SARS-CoV-2 main protease (Mpro). Molecular dynamics (MD) simulation of the NZO-S-protein-ACE-2 complex by Desmond revealed stability during 50 ns. RMSD of the NZO-S-protein-ACE-2 complex converged at 2.1 Å after 20 ns. During MD, the interaction fractions confirmed multiple interactions of NZO with Lys417, a crucial residue for inhibition of S protein. MD of DMO-Mpro complex proved its stability as the RMSD converged at 1.6 Å. Analysis of interactions during MD confirmed the interaction of Cys145 of Mpro with DMO and, thus, its inhibition. The docking predicted IC50 of NZO and DMO was 11.58 and 6.44 μM, respectively. Molecular docking and dynamics of inhibition of the S protein and Mpro by NZO and DMO correlated well. Docking of the six-hit secoiridoids to IL1R, IL6R, and TNFR1, the receptors of inflammatory cytokines IL1β, IL6, and TNFα, revealed the anti-inflammatory potential except for DHO. Due to intricate structures, the secoiridoids violated Lipinski's rule of five. However, the drug scores of secoiridoids supported their use as drugs. The ADMET predictions implied that the secoiridoids are non-toxic and pose low oral absorption. Secoiridoids need further optimization and are a suitable lead for the discovery of anti-SARS-CoV-2 therapeutics. For the moment, olive secoiridoids presents an accessible mode of prevention and therapy of SARS-CoV-2 infection.

scholarly journals Virtual Screening of Acetylcholinesterase Inhibitors Using the Lipinski’s Rule of Five and ZINC Databank

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Pablo Andrei Nogara ◽  
Rogério de Aquino Saraiva ◽  
Diones Caeran Bueno ◽  
Lílian Juliana Lissner ◽  
Cristiane Lenz Dalla Corte ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Ache Activity ◽  
Acetylcholinesterase Inhibitors ◽  
Behavioral Changes ◽  
Lipinski’S Rule ◽  
Memory Impairments ◽  
Compound C ◽  
Lipinski’S Rule Of Five

Alzheimer’s disease (AD) is a progressive and neurodegenerative pathology that can affect people over 65 years of age. It causes several complications, such as behavioral changes, language deficits, depression, and memory impairments. One of the methods used to treat AD is the increase of acetylcholine (ACh) in the brain by using acetylcholinesterase inhibitors (AChEIs). In this study, we used the ZINC databank and the Lipinski’s rule of five to perform a virtual screening and a molecular docking (using Auto Dock Vina 1.1.1) aiming to select possible compounds that have quaternary ammonium atom able to inhibit acetylcholinesterase (AChE) activity. The molecules were obtained by screening and furtherin vitroassays were performed to analyze the most potent inhibitors through the IC50value and also to describe the interaction models between inhibitors and enzyme by molecular docking. The results showed that compound D inhibited AChE activity from different vertebrate sources and butyrylcholinesterase (BChE) fromEquus ferus(EfBChE), with IC50ranging from 1.69 ± 0.46 to 5.64 ± 2.47 µM. Compound D interacted with the peripheral anionic subsite in both enzymes, blocking substrate entrance to the active site. In contrast, compound C had higher specificity as inhibitor ofEfBChE. In conclusion, the screening was effective in finding inhibitors of AChE and BuChE from different organisms.

scholarly journals Interactions of Alkyl Gallates with SARS-CoV-2 Main Protease: A Molecular Docking Approach

2020 ◽  
Vol 3 (1) ◽  
pp. 9
Author(s):  
Amalia Stefaniu ◽  
Lucia Pintilie ◽  
Bujor Albu ◽  
Lucia Pirvu
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Synthetic Compounds ◽  
X Ray ◽  
Lipinski’S Rule ◽  
Alkyl Gallates ◽  
Main Protease ◽  
Docking Approach ◽  
Lipinski’S Rule Of Five ◽  
In Silico Methods

Ten natural and semi-synthetic compounds (gallic acid and alkyl gallates) were investigated by in silico methods in order to evaluate their potential inhibitory activity against SAR-CoV-2 using the X-ray structure of SARS-CoV-2 main protease bound to Boceprevir at 1.45 Å (PDB ID: 6WNP). The evaluation of drug-likeness in terms of Lipinski’s Rule of Five and docking results in terms of docking score and interactions with the amino acids residues from the active binding site of the target protein were reported.

scholarly journals Computational analysis by molecular docking of thirty alkaloid compounds from medicinal plants as potent inhibitors of SARS-CoV-2 main protease

2021 ◽  
Vol 4 (4) ◽  
pp. 487-503
Author(s):  
Tunga Kuhana A ◽  
◽  
Jason T. Kilembe ◽  
Aristote Matondo ◽  
Khamis M. Yussuf ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Medicinal Plants ◽  
Computational Analysis ◽  
Potential Drug ◽  
Lipinski’S Rule ◽  
Main Protease ◽  
Lipinski’S Rule Of Five ◽  
Potential Inhibitors ◽  
Therapeutic Profile

Year 2020 has been highly affected by the COVID-19 outbreak. The urgent need for a potent and effective drug for the treatment of this malignancy put pressure on researchers and scientists worldwide to develop a potential drug or a vaccine to resist SARS-CoV-2 virus. We report in this paper the assessment of the efficiency of thirty alkaloid compounds derived from African medicinal plants against the SARS-CoV-2 main protease through molecular docking and bioinformatics approaches. The results revealed four potential inhibitors (ligands 18, 21, 23 and 24) with 12.26 kcal/mol being the highest binding energy. Additionally, in silico drug-likeness and ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) properties for the four ligands showed a good predicted therapeutic profile of druggability, and fully obey the Lipinski's rule of five as well.

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