scholarly journals Strategies to identify candidate repurposable drugs: COVID-19 treatment as a case example

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ali S. Imami ◽  
Robert E. McCullumsmith ◽  
Sinead M. O’Donovan
Keyword(s):  
Neurological Disorders ◽  
Drug Repurposing ◽  
Brain Disorders ◽  
Cns Disorders ◽  
Integrated Network ◽  
Innovative Strategies ◽  
Bioinformatic Tools ◽  
Bioinformatic Approaches ◽  
Novel Drug

AbstractDrug repurposing is an invaluable strategy to identify new uses for existing drug therapies that overcome many of the time and financial costs associated with novel drug development. The COVID-19 pandemic has driven an unprecedented surge in the development and use of bioinformatic tools to identify candidate repurposable drugs. Using COVID-19 as a case study, we discuss examples of machine-learning and signature-based approaches that have been adapted to rapidly identify candidate drugs. The Library of Integrated Network-based Signatures (LINCS) and Connectivity Map (CMap) are commonly used repositories and have the advantage of being amenable to use by scientists with limited bioinformatic training. Next, we discuss how these recent advances in bioinformatic drug repurposing approaches might be adapted to identify repurposable drugs for CNS disorders. As the development of novel therapies that successfully target the cause of neuropsychiatric and neurological disorders has stalled, there is a pressing need for innovative strategies to treat these complex brain disorders. Bioinformatic approaches to identify repurposable drugs provide an exciting avenue of research that offer promise for improved treatments for CNS disorders.

Identification of Antineoplastic Targets with Systems Approaches, Using Resveratrol as an In-Depth Case Study

2017 ◽  
Vol 23 (32) ◽  
pp. 4773-4793 ◽  
Author(s):  
Nivedita Singh ◽  
Sherry Freiesleben ◽  
Olaf Wolkenhauer ◽  
Yogeshwer Shukla ◽  
Shailendra K. Gupta
Keyword(s):  
Drug Target ◽  
Complex Disease ◽  
Biological Targets ◽  
Systems Approaches ◽  
Anticancer Mechanism ◽  
Genetic And Environmental Factors ◽  
Key Steps ◽  
Network Approaches ◽  
Novel Drug

The identification and validation of novel drug–target combinations are key steps in the drug discovery processes. Cancer is a complex disease that involves several genetic and environmental factors. High-throughput omics technologies are now widely available, however the integration of multi-omics data to identify viable anticancer drug-target combinations, that allow for a better clinical outcome when considering the efficacy-toxicity spectrum, is challenging. This review article provides an overview of systems approaches which help to integrate a broad spectrum of technologies and data. We focus on network approaches and investigate anticancer mechanism and biological targets of resveratrol using reverse pharmacophore mapping as an in-depth case study. The results of this case study demonstrate the use of systems approaches for a better understanding of the behavior of small molecule inhibitors in receptor binding sites. The presented network analysis approach helps in formulating hypotheses and provides mechanistic insights of resveratrol in neoplastic transformations.

Nano-Neurotherapeutics (NNTs): An Emergent and Multifaceted Tool for CNS Disorders

2020 ◽  
Vol 21 ◽  
Author(s):  
Aashish Sharma ◽  
Romila Manchanda ◽  
Faheem Hyder Pottoo ◽  
Ghulam Md. Ashraf
Keyword(s):  
Central Nervous System ◽  
Neurological Disorders ◽  
Driving Force ◽  
Treatment Options ◽  
Clinical Aspects ◽  
Future Scenarios ◽  
Cns Disorders ◽  
Drug Conjugates ◽  
Novel Treatment ◽  
Pharmacological Targets

: Impressive research steps have been taken for the treatment of neurological disorders in the last few decades. Still effective treatments of brain related disorders are very less due to problems associated with crossing the blood brain barrier (BBB), non-specific therapies, and delay in functional recovery of central nervous system (CNS) after treatment. Striving for novel treatment options for neurological disorders, nanotechnology-derived materials, and devices have gained the ground due to inherent features of derivatization/encapsulation with drugs as per the neurological ailments and pharmacological targets. Facile developments/syntheses of the nanomaterials-drug conjugates have also been the driving force for researchers to get into this field. Moreover, the tunable size and hydro/lipophilicity of these nanomaterials are the added advantages that make these materials more acceptable for CNS disorders. These nano-neurotherapeutics (NNTs) systems provide the platform for diagnosis, theranostics, treatments, restoration of CNS disorders, and encourage the translation of NNTs from “bench to bedside”. Still, these techniques are in primary stages of medical development. This review describes the latest advancements and future scenarios of developmental and clinical aspects of polymeric NNTs.

scholarly journals Associating Drugs, Targets and Clinical Outcomes into an Integrated Network Affords a New Platform for Computer-Aided Drug Repurposing

2011 ◽  
Vol 30 (2-3) ◽  
pp. 100-111 ◽  
Author(s):  
Tudor I. Oprea ◽  
Sonny Kim Nielsen ◽  
Oleg Ursu ◽  
Jeremy J. Yang ◽  
Olivier Taboureau ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Drug Repurposing ◽  
Integrated Network ◽  
Computer Aided

Innovative management strategies for building and sustaining a digital initiatives department with limited resources

2018 ◽  
Vol 34 (2) ◽  
pp. 117-136 ◽  
Author(s):  
A. Miller
Keyword(s):  
Project Management ◽  
Management Practices ◽  
Management Strategies ◽  
Academic Library ◽  
Collaborative Management ◽  
Strong Line ◽  
Content Type ◽  
Innovative Strategies ◽  
Other Information

Purpose The purpose of this paper is to offer and explore innovative strategies for building and sustaining digital initiatives at information organizations. Although the examples provided are based on case studies at an academic library, the practices are rooted in project management principles and therefore applicable to all library types, museums, archives and other information organizations. The innovative strategies on staffing and funding will be particularly useful to organizations faced with monetary and staffing shortages and highlights collaborative management practices. Design/methodology/approach Concept of strategic and collaborative management practices led by an experienced project manager cross-trained in management, technical and soft skills enables the successful development and sustainability of digital initiatives. A cross-trained librarian’s management practices of leading the Digital Scholarship Initiatives at a particular university will be examined as a case study and aided with literature supporting the need for digital initiatives leaders to have training beyond the credentials of librarian, curator, archivist or historian in the technologically savvy twenty-first century ecology of information centers. Findings The innovative strategies implemented in the case study yielded increases in the number of hours of digital lab usage, digital projects developed, seminars or workshops presented, attendance of library hosted events, number of programs implemented and awareness on campus, all with limited staff and funding. The variety and level of production and marketing is instrumental to the growth and sustainability of digital initiatives. Practical implications The innovative strategies emphasized in this paper use the concept of borrowed or shared time to start staffing needs and is particularly helpful to organizations that do not have a strong line of dedicated staffing or funding to begin building digital initiatives. Offers small ways to start immediately while setting the stage to plan for big ideas for the future. Originality/value This paper suggests a credentialed information expert, such as a librarian, archivist or curator, that is, also cross-trained in project management and technology is the key to not only successfully leading digital initiatives but is instrumental for its sustainability and the marketing, growth and future of digital initiatives.

On Integration of Additive Manufacturing During the Design and Development of a Rehabilitation Robot: A Case Study

2015 ◽  
Vol 137 (11) ◽  
Author(s):  
Kaci E. Madden ◽  
Ashish D. Deshpande
Keyword(s):  
Additive Manufacturing ◽  
Neurological Disorders ◽  
Development Process ◽  
Mechanical Design ◽  
Rehabilitation Robotics ◽  
Critical Design ◽  
Rehabilitation Robots ◽  
Time Optimization ◽  
Hand Exoskeleton

The field of rehabilitation robotics has emerged to address the growing desire to improve therapy modalities after neurological disorders, such as a stroke. For rehabilitation robots to be successful as clinical devices, a number of mechanical design challenges must be addressed, including ergonomic interactions, weight and size minimization, and cost–time optimization. We present additive manufacturing (AM) as a compelling solution to these challenges by demonstrating how the integration of AM into the development process of a hand exoskeleton leads to critical design improvements and substantially reduces prototyping cost and time.

scholarly journals Potential 2019-nCoV 3C-like Protease Inhibitors Designed Using Generative Deep Learning Approaches

2020 ◽  
Author(s):  
Alex Zhavoronkov ◽  
Vladimir Aladinskiy ◽  
Alexander Zhebrak ◽  
Bogdan Zagribelnyy ◽  
Victor Terentiev ◽  
...  
Keyword(s):  
Homology Modelling ◽  
Drug Repurposing ◽  
Hiv Protease ◽  
Learning Approaches ◽  
Protein Targets ◽  
Chemical Libraries ◽  
Internal Resources ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Novel Drug

<div> <div> <div> <p>The emergence of the 2019 novel coronavirus (2019-nCoV), for which there is no vaccine or any known effective treatment created a sense of urgency for novel drug discovery approaches. One of the most important 2019-nCoV protein targets is the 3C-like protease for which the crystal structure is known. Most of the immediate efforts are focused on drug repurposing of known clinically-approved drugs and virtual screening for the molecules available from chemical libraries that may not work well. For example, the IC50 of lopinavir, an HIV protease inhibitor, against the 3C-like protease is approximately 50 micromolar. In an attempt to address this challenge, on January 28th, 2020 Insilico Medicine decided to utilize a part of its generative chemistry pipeline to design novel drug-like inhibitors of 2019-nCoV and started generation on January 30th. It utilized three of its previously validated generative chemistry approaches: crystal-derived pocked- based generator, homology modelling-based generation, and ligand-based generation. Novel druglike compounds generated using these approaches are being published at www.insilico.com/ncov-sprint/ and will be continuously updated. Several molecules will be synthesized and tested using the internal resources; however, the team is seeking collaborations to synthesize, test, and, if needed, optimize the published molecules. </p> </div> </div> </div>

scholarly journals Network Bioinformatics Analysis Provides Insight into Drug Repurposing for COVID-2019

2020 ◽  
Author(s):  
Xu Li ◽  
Jinchao Yu ◽  
Zhiming Zhang ◽  
Jing Ren ◽  
Alex E. Peluffo ◽  
...  
Keyword(s):  
Bioinformatics Analysis ◽  
Drug Repurposing ◽  
Clinical Settings ◽  
Clinical Knowledge ◽  
Phase 3 ◽  
Module Detection ◽  
Novel Drug ◽  
Insight Into ◽  
Old Drugs ◽  
Significant Health

The COVID-2019 disease caused by the SARS-CoV-2 virus (aka 2019-nCoV) has raised significant health concerns in China and worldwide. While novel drug discovery and vaccine studies are long, repurposing old drugs against the COVID-2019 epidemic can help identify treatments, with known preclinical, pharmacokinetic, pharmacodynamic, and toxicity profiles, which can rapidly enter Phase 3 or 4 or can be used directly in clinical settings. In this study, we presented a novel network based drug repurposing platform to identify potential drugs for the treatment of COVID-2019. We first analysed the genome sequence of SARS-CoV-2 and identified SARS as the closest disease, based on genome similarity between both causal viruses, followed by MERS and other human coronavirus diseases. Using our AutoSeed pipeline (text mining and database searches), we obtained 34 COVID-2019-related genes. Taking those genes as seeds, we automatically built a molecular network for which our module detection and drug prioritization algorithms identified 24 disease-related human pathways, five modules and finally suggested 78 drugs to repurpose. Following manual filtering based on clinical knowledge, we re-prioritized 30 potential repurposable drugs against COVID-2019 (including pseudoephedrine, andrographolide, chloroquine, abacavir, and thalidomide) . We hope that this data can provide critical insights into SARS-CoV-2 biology and help design rapid clinical trials of treatments against COVID-2019.

scholarly journals Do Neurotrophins Connect Neurological Disorders and Heart Diseases?

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1730
Author(s):  
Masashi Fujitani ◽  
Yoshinori Otani ◽  
Hisao Miyajima
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cardiovascular Diseases ◽  
Cardiac Dysfunction ◽  
Neurological Disorders ◽  
Direct Evidence ◽  
Heart Diseases ◽  
Cns Disorders ◽  
New Treatment ◽  
Pituitary Adrenal Axis

Neurotrophins (NTs) are one of the most characterized neurotrophic factor family members and consist of four members in mammals. Growing evidence suggests that there is a complex inter- and bi-directional relationship between central nervous system (CNS) disorders and cardiac dysfunction, so-called “brain–heart axis”. Recent studies suggest that CNS disorders, including neurodegenerative diseases, stroke, and depression, affect cardiovascular function via various mechanisms, such as hypothalamic–pituitary–adrenal axis augmentation. Although this brain–heart axis has been well studied in humans and mice, the involvement of NT signaling in the axis has not been fully investigated. In the first half of this review, we emphasize the importance of NTs not only in the nervous system, but also in the cardiovascular system from the embryonic stage to the adult state. In the second half, we discuss the involvement of NTs in the pathogenesis of cardiovascular diseases, and then examine whether an alteration in NTs could serve as the mediator between neurological disorders and heart dysfunction. The further investigation we propose herein could contribute to finding direct evidence for the involvement of NTs in the axis and new treatment for cardiovascular diseases.

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