scholarly journals Molecular Docking and Dynamics Simulation Revealed Ivermectin as Potential Drug against Schistosoma-Associated Bladder Cancer Targeting Protein Signaling: Computational Drug Repositioning Approach

Medicina ◽  
2021 ◽  
Vol 57 (10) ◽  
pp. 1058
Author(s):  
Arif Jamal Siddiqui ◽  
Mohammad Faheem Khan ◽  
Walid Sabri Hamadou ◽  
Manish Goyal ◽  
Sadaf Jahan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Molecular Docking ◽  
Simulation Analysis ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Dynamics Simulation ◽  
Vegf Receptor ◽  
Protein Signaling ◽  
Urogenital Schistosomiasis ◽  
Potent Drug

Urogenital schistosomiasis is caused by Schistosoma haematobium (S. haematobium) infection, which has been linked to the development of bladder cancer. In this study, three repurposing drugs, ivermectin, arteether and praziquantel, were screened to find the potent drug-repurposing candidate against the Schistosoma-associated bladder cancer (SABC) in humans by using computational methods. The biology of most glutathione S-transferases (GSTs) proteins and vascular endothelial growth factor (VEGF) is complex and multifaceted, according to recent evidence, and these proteins actively participate in many tumorigenic processes such as cell proliferation, cell survival and drug resistance. The VEGF and GSTs are now widely acknowledged as an important target for antitumor therapy. Thus, in this present study, ivermectin displayed promising inhibition of bladder cancer cells via targeting VEGF and GSTs signaling. Moreover, molecular docking and molecular dynamics (MD) simulation analysis revealed that ivermectin efficiently targeted the binding pockets of VEGF receptor proteins and possessed stable dynamics behavior at binding sites. Therefore, we proposed here that these compounds must be tested experimentally against VEGF and GST signaling in order to control SABC. Our study lies within the idea of discovering repurposing drugs as inhibitors against the different types of human cancers by targeting essential pathways in order to accelerate the drug development cycle.

scholarly journals Identification of Anti-SARS-CoV-2 Compounds from Food Using QSAR-Based Virtual Screening, Molecular Docking, and Molecular Dynamics Simulation Analysis

2021 ◽  
Vol 14 (4) ◽  
pp. 357
Author(s):  
Magdi E. A. Zaki ◽  
Sami A. Al-Hussain ◽  
Vijay H. Masand ◽  
Siddhartha Akasapu ◽  
Sumit O. Bajaj ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Virtual Screening ◽  
Simulation Analysis ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Dynamics Simulation ◽  
Multilinear Regression ◽  
Qsar Analysis ◽  
Main Protease

Due to the genetic similarity between SARS-CoV-2 and SARS-CoV, the present work endeavored to derive a balanced Quantitative Structure−Activity Relationship (QSAR) model, molecular docking, and molecular dynamics (MD) simulation studies to identify novel molecules having inhibitory potential against the main protease (Mpro) of SARS-CoV-2. The QSAR analysis developed on multivariate GA–MLR (Genetic Algorithm–Multilinear Regression) model with acceptable statistical performance (R2 = 0.898, Q2loo = 0.859, etc.). QSAR analysis attributed the good correlation with different types of atoms like non-ring Carbons and Nitrogens, amide Nitrogen, sp2-hybridized Carbons, etc. Thus, the QSAR model has a good balance of qualitative and quantitative requirements (balanced QSAR model) and satisfies the Organisation for Economic Co-operation and Development (OECD) guidelines. After that, a QSAR-based virtual screening of 26,467 food compounds and 360 heterocyclic variants of molecule 1 (benzotriazole–indole hybrid molecule) helped to identify promising hits. Furthermore, the molecular docking and molecular dynamics (MD) simulations of Mpro with molecule 1 recognized the structural motifs with significant stability. Molecular docking and QSAR provided consensus and complementary results. The validated analyses are capable of optimizing a drug/lead candidate for better inhibitory activity against the main protease of SARS-CoV-2.

scholarly journals Study of Caspase 8 Inhibition for the Management of Alzheimer’s Disease: A Molecular Docking and Dynamics Simulation

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2071
Author(s):  
Syed Sayeed Ahmad ◽  
Meetali Sinha ◽  
Khurshid Ahmad ◽  
Mohammad Khalid ◽  
Inho Choi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Md Simulation ◽  
Simulation Analysis ◽  
Dynamics Simulation ◽  
Caspase 8 ◽  
Amino Acid Residues ◽  
The Stability ◽  
Molecular Docking And Dynamics

Alzheimer’s disease (AD) is the most common type of dementia and usually manifests as diminished episodic memory and cognitive functions. Caspases are crucial mediators of neuronal death in a number of neurodegenerative diseases, and caspase 8 is considered a major therapeutic target in the context of AD. In the present study, we performed a virtual screening of 200 natural compounds by molecular docking with respect to their abilities to bind with caspase 8. Among them, rutaecarpine was found to have the highest (negative) binding energy (−6.5 kcal/mol) and was further subjected to molecular dynamics (MD) simulation analysis. Caspase 8 was determined to interact with rutaecarpine through five amino acid residues, specifically Thr337, Lys353, Val354, Phe355, and Phe356, and two hydrogen bonds (ligand: H35-A: LYS353:O and A:PHE355: N-ligand: N5). Furthermore, a 50 ns MD simulation was conducted to optimize the interaction, to predict complex flexibility, and to investigate the stability of the caspase 8–rutaecarpine complex, which appeared to be quite stable. The obtained results propose that rutaecarpine could be a lead compound that bears remarkable anti-Alzheimer’s potential against caspase 8.

scholarly journals Anti Hepatitis C virus drugs show potential drug repositioning for SARS CoV-2 main protease: an in silico study

2020 ◽  
Author(s):  
Arthikasree Anandamurthy ◽  
Roslin Elsa Varughese ◽  
Saranya Sivaraj ◽  
Gayathri Dasararaju
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
In Silico ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Docking Study ◽  
Binding Potential ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Potent Drug

Abstract Developing effective and safe vaccines/drugs against SARS CoV-2 may take some time. The urgency of the outbreak has led to the usage of broad spectrum of existing anti-viral drugs, across the globe. Among the existing anti-viral drugs, there is still a challenge in identifying the potent drug or the combination of the drugs for the better treatment and faster recovery of the patients. In silico molecular docking study aids in the process of drug repurposing and we aimed to identify the binding potential of some of the existing anti-viral drugs and their interactions at the active site of SARS CoV-2 main protease. Results from our study revealed that the drugs Simeprevir, Elbasvir, Paritaprevir, Beclabuvir, Dasabuvir, Teleprevir, Velpatasvir, Ombitasvir, Ledipasvir, Boceprevir, Asunapervir, Declatasvir, Sofusbuvir which are used in the treatment of Hepatitis C virus infection may act as potent inhibitors for SARS CoV-2 main protease.

Molecular Docking and Dynamics Simulation Analysis of Thymoquinone and Thymol Compounds from Nigella sativa L. that Inhibits P38 Protein: Probable Remedies for Hepatocellular Carcinoma

2020 ◽  
Vol 16 (3) ◽  
pp. 350-357
Author(s):  
Heena Tabassum ◽  
Iffat Z. Ahmad
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Docking ◽  
Binding Energy ◽  
Simulation Analysis ◽  
Nigella Sativa ◽  
Pharmacological Action ◽  
Dynamics Simulation ◽  
Ligand Interaction ◽  
Lipinski’S Rule ◽  
Discovery Studio

Background: Currently, a novel antagonist against p38 is being designed and applied to inhibit hepatocellular carcinoma. Protein–ligand interaction plays a major role in the identification of the possible mechanism for the pharmacological action. The involvement of p38 remains an important target for anticancer drug development as its activation induces apoptosis in hepatoma cells. Objective: The aim is to identify the best candidate from the plants of N. sativa which binds with the hepatocellular carcinoma (HCC) targets by computational approach. Materials and Methods: The reported phytoconstituents such as thymoquinone and thymol present in the plant, N. sativa were docked with the HCC target such as p38. Structures of phytoconstituents were prepared using ChemDraw Ultra 10 software and converted into its 3D PDB structure and minimized using Discovery Studio client 2.5. The target protein, p38 was retrieved from RCSB PDB. Lipinski’s rule and ADMET toxicity profiling were carried out on the phytoconstituents of the N. sativa, and the compounds were further promoted for molecular docking and MD simulation analysis. Results: The docking results revealed promising inhibitory potential of thymoquinone against p38 with binding energy of -7.67 kcal/mole as compared to its known standard doxorubicin having binding energy of -6.68 kcal/mol respectively. Further, molecular dynamic (MD) simulations for 5ns were conducted for optimization, flexibility prediction, and determination of folded p38 stability. The p38-thymoquinone complex was found to be quite stable with RMSD value of 0.2 nm. Conclusion: Obtained results propose thymoquinone binding energy on the selected targets. Hence, this compound bears outstanding potential against hepatocellular carcinoma and has to be taken up for experimental work against hepatocellular carcinoma.

scholarly journals Genes Identification, Molecular Docking and Dynamics Simulation Analysis of Laccases from Amylostereum areolatum Provides Molecular Basis of Laccase Bound to Lignin

2020 ◽  
Vol 21 (22) ◽  
pp. 8845
Author(s):  
Ningning Fu ◽  
Jiaxing Li ◽  
Ming Wang ◽  
Lili Ren ◽  
Youqing Luo
Keyword(s):  
Molecular Docking ◽  
Molecular Basis ◽  
Simulation Analysis ◽  
Binding Energies ◽  
Dynamics Simulation ◽  
Amino Acid Residues ◽  
Sirex Noctilio ◽  
Mutualistic Relationship ◽  
Laccase Genes ◽  
Molecular Docking And Dynamics

An obligate mutualistic relationship exists between the fungus Amylostereum areolatum and woodwasp Sirex noctilio. The fungus digests lignin in the host pine, providing essential nutrients for the growing woodwasp larvae. However, the functional properties of this symbiosis are poorly described. In this study, we identified, cloned, and characterized 14 laccase genes from A. areolatum. These genes encoded proteins of 508 to 529 amino acids and contained three typical copper-oxidase domains, necessary to confer laccase activity. Besides, we performed molecular docking and dynamics simulation of the laccase proteins in complex with lignin compounds (monomers, dimers, trimers, and tetramers). AaLac2, AaLac3, AaLac6, AaLac8, and AaLac10 were found that had low binding energies with all lignin model compounds tested and three of them could maintain stability when binding to these compounds. Among these complexes, amino acid residues ALA, GLN, LEU, PHE, PRO, and SER were commonly present. Our study reveals the molecular basis of A. areolatum laccases interacting with lignin, which is essential for understanding how the fungus provides nutrients to S. noctilio. These findings might also provide guidance for the control of S. noctilio by informing the design of enzyme mutants that could reduce the efficiency of lignin degradation.

scholarly journals Evaluation of Drug Repositioning by Molecular Docking of Pharmaceutical Resources to Identification of Potential SARS-CoV-2 Viral Inhibitors

2022 ◽  
Author(s):  
Fatemeh Hosseini ◽  
Mehrdad Azin ◽  
Hamideh Ofoghi ◽  
Tahereh Alinejad
Keyword(s):  
Molecular Docking ◽  
Drug Discovery ◽  
In Silico ◽  
De Novo ◽  
Drug Repositioning ◽  
Antiviral Drug ◽  
Drug Repurposing ◽  
Future Perspective

Unfortunately, to date, there is no approved specific antiviral drug treatment against COVID-19. Due to the costly and time-consuming nature of the de novo drug discovery and development process, in recent days, the computational drug repositioning method has been highly regarded for accelerating the drug-discovery process. The selection of drug target molecule(s), preparation of an approved therapeutics agent library, and in silico evaluation of their affinity to the subjected target(s) are the main steps of a molecular docking-based drug repositioning process, which is the most common computational drug re-tasking process. In this chapter, after a review on origin, pathophysiology, molecular biology, and drug development strategies against COVID-19, recent advances, challenges as well as the future perspective of molecular docking-based drug repositioning for COVID-19 are discussed. Furthermore, as a case study, the molecular docking-based drug repurposing process was planned to screen the 3CLpro inhibitor(s) among the nine Food and Drug Administration (FDA)-approved antiviral protease inhibitors. The results demonstrated that Fosamprenavir had the highest binding affinity to 3CLpro and can be considered for more in silico, in vitro, and in vivo evaluations as an effective repurposed anti-COVID-19 drug.

Recent Advances in Drug Repurposing for Parkinson’s Disease

2019 ◽  
Vol 26 (28) ◽  
pp. 5340-5362 ◽  
Author(s):  
Xin Chen ◽  
Giuseppe Gumina ◽  
Kristopher G. Virga
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Discovery ◽  
De Novo ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Cost Effective ◽  
New Drugs ◽  
Recent Advances ◽  
Clinical Drugs

:As a long-term degenerative disorder of the central nervous system that mostly affects older people, Parkinson’s disease is a growing health threat to our ever-aging population. Despite remarkable advances in our understanding of this disease, all therapeutics currently available only act to improve symptoms but cannot stop the disease progression. Therefore, it is essential that more effective drug discovery methods and approaches are developed, validated, and used for the discovery of disease-modifying treatments for Parkinson’s disease. Drug repurposing, also known as drug repositioning, or the process of finding new uses for existing or abandoned pharmaceuticals, has been recognized as a cost-effective and timeefficient way to develop new drugs, being equally promising as de novo drug discovery in the field of neurodegeneration and, more specifically for Parkinson’s disease. The availability of several established libraries of clinical drugs and fast evolvement in disease biology, genomics and bioinformatics has stimulated the momentums of both in silico and activity-based drug repurposing. With the successful clinical introduction of several repurposed drugs for Parkinson’s disease, drug repurposing has now become a robust alternative approach to the discovery and development of novel drugs for this disease. In this review, recent advances in drug repurposing for Parkinson’s disease will be discussed.

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