scholarly journals Galaxy workflows for fragment-based virtual screening: a case study on the SARS-CoV-2 main protease

2021 ◽  
Author(s):  
Simon Bray ◽  
Tim Dudgeon ◽  
Rachael Skyner ◽  
Rolf Backofen ◽  
Björn Grüning ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Workflow Management ◽  
Ligand Docking ◽  
Energy Calculation ◽  
Command Line ◽  
Graphical Interface ◽  
Public Infrastructure ◽  
Main Protease ◽  
The Subject

We present several workflows for protein-ligand docking and free energy calculation for use in the workflow management system Galaxy. The workflows are composed of several widely used open-source tools, including rDock and GROMACS, and can be executed on public infrastructure using either Galaxy's graphical interface or the command line. We demonstrate the utility of the workflows by running a high-throughput virtual screening of around 40000 compounds against the SARS-CoV-2 main protease, a system which has been the subject of intense study in the last year.

scholarly journals Repurposing of FDA approved drugs targeting Main protease MPro for SARS-CoV-2

2020 ◽  
Author(s):  
Suryakant Tiwari ◽  
Raghav Jain ◽  
Indrani Banerjee
Keyword(s):  
Drug Discovery ◽  
Virtual Screening ◽  
Active Site ◽  
Ligand Docking ◽  
Kcal Mole ◽  
Main Protease ◽  
Alternative Approach ◽  
Repurposed Drugs ◽  
Approved Drugs ◽  
Fda Approved Drugs

Abstract SARS-CoV-2 is one of the greatest pandemics in the history. There is no medicine or vaccine yet discovered to control the outbreak. The paper deals with repurposing existing drugs to control the outbreak of SARS-CoV-2 virus.Ten FDA-approved drugs namely Indinavir, Nelfinavir, Letermovir, Irinotecan, Elbasvir, Saquinavir, Darunavir, Raltegravir, Atazanavir and Amprenavir were studied. In silico methods for virtual screening of protein-ligand docking of these drugs against SARS-CoV-2 MPro was performed. The binding efficiency of the drugs against viral main protease MPro was significantly high to inhibit SARS-CoV-2.The results confirmed that Atazanavir, Nelfinavir, and Letermovir not only occupied the active site of Mpro but also showed increased binding affinity (-10.36 kcal/mole, -9.47 kcal/mole and -9.43 kcal/mole) even more than of control drugs of Lopinavir (-8.71 kcal/mole) and Ritonavir (-8.08 kcal/mole). These repurposed drugs can be used in combination or individually as an alternative approach for rapid drug discovery against SARS-CoV-2

Machine Learning-based Virtual Screening Strategy Reveals Some Natural Compounds As Potential PAK4 Inhibitors In Triple Negative Breast Cancer

2020 ◽  
Vol 18 ◽  
Author(s):  
Opeyemi Iwaloye ◽  
Olusola Olalekan Elekofehinti ◽  
Babatomiwa Kikiowo ◽  
Emmanuel Ayo Oluwarotimi ◽  
Toyin Mary Fadipe
Keyword(s):  
Breast Cancer ◽  
Virtual Screening ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Binding Free Energy ◽  
Natural Compounds ◽  
Energy Calculation ◽  
Reference Drug ◽  
Predictive Quality

Background: P-21 activating kinase 4 (PAK4) is implicated in poor prognosis of many cancers, especially in the progression of Triple Negative Breast Cancer (TNBC). The present study was aimed at designing some potential drug candidates as PAK4 inhibitors for breast cancer therapy. Objective: This study aimed to finding novel inhibitors of PAK4 from natural compounds using computational approach. Methods: An e-pharmacophore model was developed from docked PAK4-coligand complex and used to screen over a thousand natural compounds downloaded from BIOFACQUIM and NPASS databases to match a minimum of 5 sites for selected (ADDDHRR) hypothesis. The robustness of the virtual screening method was accessed by well-established methods including EF, ROC, BEDROC, AUAC, and the RIE. Compounds with fitness score greater than one were filtered by applying molecular docking (HTVS, SP, XP and Induced fit docking) and ADME prediction. Using Machine learningbased approach QSAR model was generated using Automated QSAR. The computed top model kpls_des_17 (R2= 0.8028, RMSE = 0.4884 and Q2 = 0.7661) was used to predict the pIC50 of the lead compounds. Internal and external validations were accessed to determine the predictive quality of the model. Finally the binding free energy calculation was computed. Results: The robustness/predictive quality of the models were affirmed. The hits had better binding affinity than the reference drug and interacted with key amino acids for PAK4 inhibition. Overall, the present analysis yielded three potential inhibitors that are predicted to bind with PAK4 better than reference drug tamoxifen. The three potent novel inhibitors vitexin, emodin and ziganein recorded IFD score of -621.97 kcal/mol, -616.31 kcal/mol and -614.95 kcal/mol, respectively while showing moderation for ADME properties and inhibition constant. Conclusion: It is expected that the findings reported in this study may provide insight for designing effective and less toxic PAK4 inhibitors for triple negative breast cancer.

Virtual Screening, Molecular docking and in-silico ADME-Tox analysis for identification of potential main protease (Mpro) enzyme inhibitors

2020 ◽  
Vol 18 ◽  
Author(s):  
Debadash Panigrahi ◽  
Ganesh Prasad Mishra
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
In Silico ◽  
Data Bank ◽  
Future Research ◽  
Reference Compound ◽  
Unexpected Death ◽  
Main Protease ◽  
In Silico Admet

Objective:: Recent pandemic caused by SARS-CoV-2 described in Wuhan China in December-2019 spread widely almost all the countries of the world. Corona virus (COVID-19) is causing the unexpected death of many peoples and severe economic loss in several countries. Virtual screening based on molecular docking, drug-likeness prediction, and in silico ADMET study has become an effective tool for the identification of small molecules as novel antiviral drugs to treat diseases. Methods:: In the current study, virtual screening was performed through molecular docking for identifying potent inhibitors against Mpro enzyme from the ZINC library for the possible treatment of COVID-19 pandemic. Interestingly, some compounds are identified as possible anti-covid-19 agents for future research. 350 compounds were screened based on their similarity score with reference compound X77 from ZINC data bank and were subjected to docking with crystal structure available of Mpro enzyme. These compounds were then filtered by their in silico ADME-Tox and drug-likeness prediction values. Result:: Out of these 350 screened compounds, 10 compounds were selected based on their docking score and best docked pose in comparison to the reference compound X77. In silico ADME-Tox and drug likeliness predictions of the top compounds were performed and found to be excellent results. All the 10 screened compounds showed significant binding pose with the target enzyme main protease (Mpro) enzyme and satisfactory pharmacokinetic and toxicological properties. Conclusion:: Based on results we can suggest that the identified compounds may be considered for therapeutic development against the COVID-19 virus and can be further evaluated for in vitro activity, preclinical, clinical studies and formulated in a suitable dosage form to maximize their bioavailability.

Polytechnic to Business Project (P2B) a Case of Innovation and Knowledge Transference

2019 ◽  
Vol 6 (1) ◽  
pp. 40-49
Author(s):  
Teresa Paiva
Keyword(s):  
Knowledge Transfer ◽  
Best Practices ◽  
Education Institution ◽  
Theoretical Background ◽  
Transfer Model ◽  
Case Study Method ◽  
Multiple Sources ◽  
The Subject ◽  
Manage Innovation

Background: The theoretical background of this article is on the model developed of knowledge transfer between universities and the industry in order to access the best practices and adapt to the study case in question regarding the model of promoting and manage innovation within the universities that best contribute with solution and projects to the business field. Objective: The development of a knowledge transfer model is the main goal of this article, supported in the best practices known and, also, to reflect in the main measurement definitions to evaluate the High Education Institution performance in this area. Methods: The method for this article development is the case study method because it allows the fully understanding of the dynamics present within a single setting, and the subject examined to comprehend what is being done and what the dynamics mean. The case study does not have a data collection method, as it is a research that may rely on multiple sources of evidence and data which should be converged. Results: Since it’s a case study this article present a fully description of the model proposed and implemented for the knowledge transfer process of the institution. Conclusion: Still in a discussion phase, this article presents as conclusions some questions and difficulties that could be pointed out, as well as some good perspectives of performed activity developed.

An Ayurvedic Visual Rehabilitation In Lebers Congenital Amaurosis - Prospective Case Study

2018 ◽  
Vol 3 (4) ◽  
Author(s):  
Dr. Vidhyasri M ◽  
Dr. S. M. Pasha
Keyword(s):  
Marked Improvement ◽  
Clinical Case ◽  
Treatment Plan ◽  
Visual Disability ◽  
Visual Rehabilitation ◽  
Potential Risks ◽  
The Subject ◽  
Slow Frequency

Introduction: This is the case report of child who was diagnosed with LCA reported with complaints of large-amplitude, slow-frequency, roving nystagmus, frequent tendency to press on his eyes, enopthalmos, with completely normal ophthalmoscopic examination with normal appearing optic nerve and retina and has a non recordable ERG; considering this condition under the lines of Vataja Nanatmaja Vyadhi treatment was structured to render effective visual rehabilitation which showed marked results. Methods: 4 years old male child who was diagnosed with lebers congenital amaurosis was brought by his parents to Eye OPD, GAMC, Bengaluru. The presentation of this case includes bibliographic review of the subject, presentation of a clinical case and description of the importance of Ayurvedic prespective of handling of these patients. Results: The child showed improvement in fixing for light and also nystagmus showed marked improvement and there were considerable behavioural changes observed. Discussion: It is important to deepen the environment of the disease to know the possible implications in Ayurvedic management, recognize the magnitude of visual disability that our patient presents for the establishment of the treatment plan and provide an integral care of excellence in an interdisciplinary way in favor of visual rehabilitation of our patients and also help to restore quality of life with no potential risks of side effects.

scholarly journals Techniques for Mitigating the Effects of Smoke Taint While Maintaining Quality in Wine Production: A Review

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1672
Author(s):  
Ysadora A. Mirabelli-Montan ◽  
Matteo Marangon ◽  
Antonio Graça ◽  
Christine M. Mayr Marangon ◽  
Kerry L. Wilkinson
Keyword(s):  
Global Perspective ◽  
Wine Industry ◽  
Wine Production ◽  
Specific Data ◽  
Main Research ◽  
Initial Severity ◽  
The Subject ◽  
Available Information

Smoke taint has become a prominent issue for the global wine industry as climate change continues to impact the length and extremity of fire seasons around the world. Although the issue has prompted a surge in research on the subject in recent years, no singular solution has yet been identified that is capable of maintaining the quality of wine made from smoke-affected grapes. In this review, we summarize the main research on smoke taint, the key discoveries, as well as the prevailing uncertainties. We also examine methods for mitigating smoke taint in the vineyard, in the winery, and post production. We assess the effectiveness of remediation methods (proposed and actual) based on available research. Our findings are in agreement with previous studies, suggesting that the most viable remedies for smoke taint are still the commercially available activated carbon fining and reverse osmosis treatments, but that the quality of the final treated wines is fundamentally dependent on the initial severity of the taint. In this review, suggestions for future studies are introduced for improving our understanding of methods that have thus far only been preliminarily investigated. We select regions that have already been subjected to severe wildfires, and therefore subjected to smoke taint (particularly Australia and California) as a case study to inform other wine-producing countries that will likely be impacted in the future and suggest specific data collection and policy implementation actions that should be taken, even in countries that have not yet been impacted by smoke taint. Ultimately, we streamline the available information on the topic of smoke taint, apply it to a global perspective that considers the various stakeholders involved, and provide a launching point for further research on the topic.

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.

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