scholarly journals The COVID-19 PHARMACOME: Rational Selection of Drug Repurposing Candidates from Multimodal Knowledge Harmonization

2020 ◽  
Author(s):  
Bruce Schultz ◽  
Andrea Zaliani ◽  
Christian Ebeling ◽  
Jeanette Reinshagen ◽  
Denisa Bojkova ◽  
...  
Keyword(s):  
Drug Target ◽  
Systematic Approach ◽  
Drug Repurposing ◽  
Global Scale ◽  
Rational Selection ◽  
Related Information ◽  
Singular Source ◽  
Therapeutic Compounds ◽  
Selection Of ◽  
Made In

AbstractThe SARS-CoV-2 pandemic has challenged researchers at a global scale. The scientific community’s massive response has resulted in a flood of experiments, analyses, hypotheses, and publications, especially in the field drug repurposing. However, many of the proposed therapeutic compounds obtained from SARS-CoV-2 specific assays are not in agreement and thus demonstrate the need for a singular source of COVID-19 related information from which a rational selection of drug repurposing candidates can be made. In this paper, we present the COVID-19 PHARMACOME, a comprehensive drug-target-mechanism graph generated from a compilation of several disease maps and experimental data focused on SARS-CoV-2 / COVID-19 pathophysiology. By applying a systematic approach, we were able to predict the effect of drug pairs on SARS-CoV-2 infection. Experimental validation of our results demonstrate that our graph can be used to not only explore the involved mechanistic pathways, but also to identify novel combinations of drug repurposing candidates.

scholarly journals A method for the rational selection of drug repurposing candidates from multimodal knowledge harmonization

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bruce Schultz ◽  
Andrea Zaliani ◽  
Christian Ebeling ◽  
Jeanette Reinshagen ◽  
Denisa Bojkova ◽  
...  
Keyword(s):  
Drug Target ◽  
Systematic Approach ◽  
Drug Repurposing ◽  
Global Scale ◽  
Rational Selection ◽  
Related Information ◽  
Singular Source ◽  
Therapeutic Compounds ◽  
Selection Of ◽  
Made In

AbstractThe SARS-CoV-2 pandemic has challenged researchers at a global scale. The scientific community’s massive response has resulted in a flood of experiments, analyses, hypotheses, and publications, especially in the field of drug repurposing. However, many of the proposed therapeutic compounds obtained from SARS-CoV-2 specific assays are not in agreement and thus demonstrate the need for a singular source of COVID-19 related information from which a rational selection of drug repurposing candidates can be made. In this paper, we present the COVID-19 PHARMACOME, a comprehensive drug-target-mechanism graph generated from a compilation of 10 separate disease maps and sources of experimental data focused on SARS-CoV-2/COVID-19 pathophysiology. By applying our systematic approach, we were able to predict the synergistic effect of specific drug pairs, such as Remdesivir and Thioguanosine or Nelfinavir and Raloxifene, on SARS-CoV-2 infection. Experimental validation of our results demonstrate that our graph can be used to not only explore the involved mechanistic pathways, but also to identify novel combinations of drug repurposing candidates.

scholarly journals Guidelines for Developing Yoga Interventions for Randomized Trials

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Karen J. Sherman
Keyword(s):  
Randomized Trials ◽  
Systematic Approach ◽  
Total Duration ◽  
Treatment Protocols ◽  
Breathing Exercises ◽  
Protocol Development ◽  
Specific Protocol ◽  
Key Issues ◽  
Selection Of ◽  
Made In

Little guidance is available to assist researchers in developing treatment protocols for research on yoga for health concerns. Because yoga is a complex multifactorial mind-body discipline historically developed for nonmedical purposes, numerous decisions must be made in order to thoughtfully develop such protocols. In this paper, a systematic approach is proposed to assist researchers in selecting an intervention that is appropriate for the condition under consideration and explicitly developed. Researchers need to consider the type or “style” of yoga, the components to include (e.g., breathing exercises, postures) as well as the specific protocol for each component, the dose to be delivered (frequency, duration of practice, and the total duration of practice), and issues related to selection of instructors and monitoring the fidelity to the intervention. Each of these domains and the key issues for the development of protocols is discussed. Finally, some areas for further research related to protocol development are recommended.

scholarly journals Drug repurposing screening identified tropifexor as a SARS-CoV-2 papain-like protease inhibitor

2021 ◽  
Author(s):  
Chunlong Ma ◽  
Yuyin Wang ◽  
Juliana Choza ◽  
Jun Wang
Keyword(s):  
Drug Target ◽  
Drug Repurposing ◽  
Fold Increase ◽  
Bioactive Compound ◽  
Compound Library ◽  
High Profile ◽  
Main Protease ◽  
Viral Polyprotein ◽  
Dose Dependent ◽  
Made In

AbstractThe global COVID-19 pandemic underscores the dire need of effective antivirals. Encouraging progress has been made in developing small molecule inhibitors targeting the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and main protease (Mpro). However, the development of papain-like protease (PLpro) inhibitors faces several obstacles. Nevertheless, PLpro represents a high-profile drug target given its multifaceted roles in viral replication. PLpro is involved in not only the cleavage of viral polyprotein but also modulation of host immune response. In this study, we conducted a drug-repurposing screening of PLpro against the MedChemExpress bioactive compound library and identified three hits, EACC, KY-226, and tropifexor, as potent PLpro inhibitors with IC50 values ranging from 3.39 to 8.28 µM. The three hits showed dose-dependent binding to PLpro in the thermal shift assay. In addition, tropifexor inhibited the cellular PLpro activity in the FlipGFP assay with an IC50 of 10.6 µM. Gratifyingly, tropifexor showed antiviral activity against SARS-CoV-2 in Calu-3 cells with an EC50 of 4.03 µM, a 7.8-fold increase compared to GRL0617 (EC50 = 31.4 µM). Overall, tropifexor represents a novel PLpro inhibitor that can be further developed as SARS-CoV-2 antivirals.

Rapid Elaboration of Fragments into Leads Applied to Bromodomain-3 Extra Terminal Domain

2020 ◽  
Author(s):  
Luke Adams ◽  
Lorna E. Wilkinson-White ◽  
Menachem J. Gunzburg ◽  
Stephen J. Headey ◽  
Martin J. Scanlon ◽  
...  
Keyword(s):  
Binding Site ◽  
Systematic Approach ◽  
Structural Information ◽  
Peptide Binding ◽  
Chemical Diversity ◽  
Chemical Probes ◽  
Protein Targets ◽  
Structure Activity ◽  
Peptide Binding Site ◽  
Selection Of

The development of low-affinity fragment hits into higher affinity leads is a major hurdle in fragment-based drug design. Here we demonstrate an approach for the Rapid Elaboration of Fragments into Leads (REFiL) applying an integrated workflow that provides a systematic approach to generate higher-affinity binders without the need for structural information. The workflow involves the selection of commercial analogues of fragment hits to generate preliminary structure-activity relationships. This is followed by parallel microscale chemistry using chemoinformatically designed reagent libraries to rapidly explore chemical diversity. Upon completion of a fragment screen against Bromodomain-3 extra terminal (BRD3-ET) domain we applied the REFiL workflow, which allowed us to develop a series of tetrahydrocarbazole ligands that bind to the peptide binding site of BRD3-ET. With REFiL we were able to rapidly improve binding affinity >30-fold. The REFiL workflow can be applied readily to a broad range of protein targets without the need of a structure, allowing the efficient evolution of low-affinity fragments into higher affinity leads and chemical probes.<br>

WINTER WHEAT DEVELOPED BY THE UDMURT RESEARCH INSTITUTE OF AGRICULTURE IN COMPETITIVE VARIETY TESTING

2020 ◽  
pp. 5-16
Author(s):  
I.V. TORBINA ◽  
◽  
I.R. FARDEYEVA ◽  
Keyword(s):  
Winter Wheat ◽  
Crop Rotation ◽  
Biological Characteristics ◽  
Commercial Use ◽  
Breeding Material ◽  
Rotation Pattern ◽  
Selection Of ◽  
Variety Testing ◽  
Made In ◽  
Research Institute

The paper assesses the promising varieties of winter wheat in a competitive variety test by the main economic and biological characteristics that determine the suitability of the variety for commercial use. The object of research was the authors’ own breeding material. The experiments on the selection of winter wheat were made in the experimental crop rotation pattern of the Institute.

Evidence-based Assessment

2010 ◽  
pp. 76-98
Author(s):  
John Hunsley ◽  
Eric J. Mash
Keyword(s):  
Decision Making ◽  
Clinical Assessment ◽  
Assessment Process ◽  
Evidence Based ◽  
The Past ◽  
Specific Assessment ◽  
The Many ◽  
Selection Of ◽  
Made In

Evidence-based assessment relies on research and theory to inform the selection of constructs to be assessed for a specific assessment purpose, the methods and measures to be used in the assessment, and the manner in which the assessment process unfolds. An evidence-based approach to clinical assessment necessitates the recognition that, even when evidence-based instruments are used, the assessment process is a decision-making task in which hypotheses must be iteratively formulated and tested. In this chapter, we review (a) the progress that has been made in developing an evidence-based approach to clinical assessment in the past decade and (b) the many challenges that lie ahead if clinical assessment is to be truly evidence-based.

scholarly journals The use of cement concrete pavements for roads, depending on climatic conditions

2019 ◽  
Vol 13 (3) ◽  
pp. 235-240
Author(s):  
Iryna Solonenko
Keyword(s):  
European Union ◽  
Statistical Models ◽  
Road Network ◽  
The European Union ◽  
Rational Selection ◽  
Cement Concrete ◽  
The Road ◽  
Road Pavement ◽  
Operational Characteristics ◽  
Selection Of

The development of road network infrastructure is an important component of the economic development of the European Union. Updating of the road network contributes to the integration of the economies of countries into a coherent whole. The road network provides the free movement of citizens, the movement of goods and the effective implementation of various services. The increase in the length of the road network leads to an increase in the financial and material costs necessary to ensure its maintenance and repair. One of the ways to reduce costs is by strengthening the physic-mechanical and operational characteristics of the pavement due to the widespread use of cement concrete. The quality of the pavement of cement concrete depends largely on the rational selection of its composition. This allows a significant increase in the durability of road pavement. The purpose of the research was: the development of recommendations for the rational selection of the composition of the road pavement material of cement concrete, aimed at upgrading longevity, and taking into account its frost resistance grade. According to the goal, the following tasks were developed: the analyses of the climatic zones in which the road network of the European Union is located; the development of a research plan, a selection of the response function and influence factors; the study of physico-mechanical and operational characteristics of the researched material of road pavement; on the basis of the obtained data, the calculation of the complex of experimental-statistical models, which describe the physico-mechanical and operational characteristics of the road pavement material; on the basis of experimental statistical models, a method was proposed for selecting the rational compositions of the cement concrete pavement road material depending on the conditions of its application. The results presented in the article can be used in engineering and scientific practice for the selection of road pavement from cement concrete for highways.

scholarly journals NOD: a web server to predict New use of Old Drugs to facilitate drug repurposing

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tarun Jairaj Narwani ◽  
Narayanaswamy Srinivasan ◽  
Sohini Chakraborti
Keyword(s):  
Chemical Space ◽  
Web Server ◽  
Drug Repurposing ◽  
Cost Effective ◽  
Evolutionary Information ◽  
Cost Effective Alternative ◽  
Similarity Searches ◽  
Old Drugs ◽  
Control Study ◽  
Made In

AbstractComputational methods accelerate the drug repurposing pipelines that are a quicker and cost-effective alternative to discovering new molecules. However, there is a paucity of web servers to conduct fast, focussed, and customized investigations for identifying new uses of old drugs. We present the NOD web server, which has the mentioned characteristics. NOD uses a sensitive sequence-guided approach to identify close and distant homologs of a protein of interest. NOD then exploits this evolutionary information to suggest potential compounds from the DrugBank database that can be repurposed against the input protein. NOD also allows expansion of the chemical space of the potential candidates through similarity searches. We have validated the performance of NOD against available experimental and/or clinical reports. In 65.6% of the investigated cases in a control study, NOD is able to identify drugs more effectively than the searches made in DrugBank. NOD is freely-available at http://pauling.mbu.iisc.ac.in/NOD/NOD/.

scholarly journals A Clinical Study to Correlate the Facial Form and Maxillary Central Incisor Tooth Form in Males and Females of Davangere Population

2016 ◽  
Vol 04 (03) ◽  
pp. 156-164
Author(s):  
Deepak Bansal ◽  
Shruti Sharma ◽  
Manjit Kumar ◽  
Amrit Khosla
Keyword(s):  
Facial Appearance ◽  
Central Incisor ◽  
Incisor Tooth ◽  
Maxillary Central Incisor ◽  
Anterior Teeth ◽  
The Face ◽  
Tooth Form ◽  
Males And Females ◽  
Selection Of ◽  
Made In

AbstractAn altered facial appearance is more difficult to face, than problems related to ill-fitting denture or eating. The selection of maxillary anterior teeth for complete denture has long posed problem in clinical practice and a controversy about the best method to employ still exists. An attempt is made in the present study to clinically correlate the face form with maxillary central incisor tooth form in males and females of Davangere population. In 1914, Leon William's projected the “the form method” where he classified facial forms as square, tapering, and ovoid. Maxillary central incisors were selected according to the facial forms.Of total 100 subjects four different tooth forms and face forms were evaluated. They are: square, ovoid, square-tapered, tapered. No significant correlation existed between face form in male and females. Females exhibited greater correlation between face forms and inverted tooth form but that correlation is not sufficient to serve as a guide for selection of anterior teeth.

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