scholarly journals Open drug discovery of anti-virals critical for Canada’s pandemic strategy

FACETS ◽  
2020 ◽  
Vol 5 (1) ◽  
pp. 1019-1036
Author(s):  
Tania Bubela ◽  
E. Richard Gold ◽  
Vivek Goel ◽  
Max Morgan ◽  
Karen Mossman ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Drug Discovery ◽  
Transaction Costs ◽  
Low Cost ◽  
Open Science ◽  
Regulatory Mechanisms ◽  
High Quality ◽  
Science Practices ◽  
Fundamental Research ◽  
Oriented Research

In the event of the current COVID-19 pandemic and in preparation for future pandemics, open science can support mission-oriented research and development, as well as commercialization. Open science shares skills and resources across sectors; avoids duplication and provides the basis for rapid and effective validation due to full transparency. It is a strategy that can adjust quickly to reflect changing incentives and priorities, because it does not rely on any one actor or sector. While eschewing patents, it can ensure high-quality drugs, low pricing, and access through existing regulatory mechanisms. Open science practices and partnerships decrease transaction costs, increase diversity of actors, reduce overall costs, open new, higher-risk/higher-impact approaches to research, and provide entrepreneurs freedom to operate and freedom to innovate. We argue that it is time to re-open science, not only in its now restricted arena of fundamental research, but throughout clinical translation. Our model and attendant recommendations map onto a strategy to accelerate discovery of novel broad-spectrum anti-viral drugs and clinical trials of those drugs, from first-in-human safety-focused trials to late stage trials for efficacy. The goal is to ensure low-cost and rapid access, globally, and to ensure that Canadians do not pay a premium for drugs developed from Canadian science.

scholarly journals A pocket guide on how to structure SARS-CoV-2 drugs and therapies

2020 ◽  
Vol 48 (6) ◽  
pp. 2625-2641
Author(s):  
Dene R. Littler ◽  
Bruce J. MacLachlan ◽  
Gabrielle M. Watson ◽  
Julian P. Vivian ◽  
Benjamin S. Gully
Keyword(s):  
Clinical Trials ◽  
Drug Discovery ◽  
Viral Replication ◽  
Structural Biology ◽  
Successful Treatment ◽  
Replication Cycle ◽  
Structural Studies ◽  
Fundamental Research ◽  
Public Repositories ◽  
Structural Homologue

The race to identify a successful treatment for COVID19 will be defined by fundamental research into the replication cycle of the SARS-CoV-2 virus. This has identified five distinct stages from which numerous vaccination and clinical trials have emerged alongside an innumerable number of drug discovery studies currently in development for disease intervention. Informing every step of the viral replication cycle has been an unprecedented ‘call-to-arms' by the global structural biology community. Of the 20 main SARS-CoV-2 proteins, 13 have been resolved structurally for SARS-CoV-2 with most having a related SARS-CoV and MERS-CoV structural homologue totalling some 300 structures currently available in public repositories. Herein, we review the contribution of structural studies to our understanding of the virus and their role in structure-based development of therapeutics.

From transaction costs to transaction value: Overcoming the frictional paradigm

2020 ◽  
pp. 51-81
Author(s):  
D. P. Frolov
Keyword(s):  
Transaction Costs ◽  
Transaction Cost ◽  
Path Dependence ◽  
Transaction Cost Economics ◽  
Cost Minimization ◽  
Low Cost ◽  
Coase Theorem ◽  
Transactional Analysis ◽  
Transaction Sector ◽  
Transaction Value

The transaction cost economics has accumulated a mass of dogmatic concepts and assertions that have acquired high stability under the influence of path dependence. These include the dogma about transaction costs as frictions, the dogma about the unproductiveness of transactions as a generator of losses, “Stigler—Coase” theorem and the logic of transaction cost minimization, and also the dogma about the priority of institutions providing low-cost transactions. The listed dogmas underlie the prevailing tradition of transactional analysis the frictional paradigm — which, in turn, is the foundation of neo-institutional theory. Therefore, the community of new institutionalists implicitly blocks attempts of a serious revision of this dogmatics. The purpose of the article is to substantiate a post-institutional (alternative to the dominant neo-institutional discourse) value-oriented perspective for the development of transactional studies based on rethinking and combining forgotten theoretical alternatives. Those are Commons’s theory of transactions, Wallis—North’s theory of transaction sector, theory of transaction benefits (T. Sandler, N. Komesar, T. Eggertsson) and Zajac—Olsen’s theory of transaction value. The article provides arguments and examples in favor of broader explanatory possibilities of value-oriented transactional analysis.

Sitagliptin: a potential drug for the treatment of SARS-CoV-2?

2020 ◽  
Author(s):  
Sanaa Bardaweel
Keyword(s):  
Clinical Trials ◽  
Drug Discovery ◽  
Antimalarial Drug ◽  
Drug Repurposing ◽  
Spike Protein ◽  
Diabetic Patients ◽  
Potential Drug ◽  
Chemokine Production ◽  
Drug Discovery And Development ◽  
Sequence Identity

Recently, an outbreak of fatal coronavirus, SARS-CoV-2, has emerged from China and is rapidly spreading worldwide. As the coronavirus pandemic rages, drug discovery and development become even more challenging. Drug repurposing of the antimalarial drug chloroquine and its hydroxylated form had demonstrated apparent effectiveness in the treatment of COVID-19 associated pneumonia in clinical trials. SARS-CoV-2 spike protein shares 31.9% sequence identity with the spike protein presents in the Middle East Respiratory Syndrome Corona Virus (MERS-CoV), which infects cells through the interaction of its spike protein with the DPP4 receptor found on macrophages. Sitagliptin, a DPP4 inhibitor, that is known for its antidiabetic, immunoregulatory, anti-inflammatory, and beneficial cardiometabolic effects has been shown to reverse macrophage responses in MERS-CoV infection and reduce CXCL10 chemokine production in AIDS patients. We suggest that Sitagliptin may be beneficial alternative for the treatment of COVID-19 disease especially in diabetic patients and patients with preexisting cardiovascular conditions who are already at higher risk of COVID-19 infection.

Prerequisites to support high-quality clinical trials in children and young people

2020 ◽  
pp. archdischild-2019-318677
Author(s):  
Steven Hirschfeld ◽  
Florian B Lagler ◽  
Jenny M Kindblom
Keyword(s):  
Clinical Trials ◽  
Healthcare Delivery ◽  
Paediatric Population ◽  
Ecosystem Functions ◽  
Healthcare Delivery System ◽  
High Quality ◽  
Children And Young People ◽  
The Right ◽  
Support Decision Making

Children have the right to treatment based on the same quality of information that guides treatment in adults. Without the proper evaluation of medicinal products and devices in paediatric clinical trials that are designed to meet the rigorous standards of the competent authorities, children are discriminated from advances in medicine. There are regulatory, scientific and ethical incentives to address the knowledge gap regarding efficacy and safety of medicines in the paediatric population. High-quality clinical trials involving children of all ages can generate data that will ultimately close the knowledge gaps and support decision making.For clinical trials that enrol children, the needs are specialised and often resource intensive. Prerequisites for successful paediatric clinical trials are personnel with training in both paediatrics and neonatology and expertise in clinical trials in these populations. Moreover, national and international networks for efficient collaboration, dissemination of information, and sharing of resources and expertise are also needed, together with competent, efficient and high-quality local infrastructure with effective processes. Monitoring and oversight bodies with the relevant competence, including expertise in paediatrics, is also an important prerequisite for paediatric clinical trials. Compromise in any of these components will compromise the downstream results.This paper discusses the structures and competences needed in order to perform effective, high-quality paediatric clinical trials with the ultimate goal of better medicines and treatments for children. We propose a model of examining the process as a series of components that each has to be optimised, then all the components are actively optimised to function together as an ecosystem, and the resulting ecosystem functions well with the general research system and the healthcare delivery system.

scholarly journals In silico imaging clinical trials: cheaper, faster, better, safer, and more scalable

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Aldo Badano
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Medical Devices ◽  
In Silico ◽  
Lessons Learned ◽  
Patient Access ◽  
High Quality ◽  
Virtual Imaging ◽  
Regulatory Evaluation

AbstractImaging clinical trials can be burdensome and often delay patient access to novel, high-quality medical devices. Tools for in silico imaging trials have significantly improved in sophistication and availability. Here, I describe some of the principal advantages of in silico imaging trials and enumerate five lessons learned during the design and execution of the first all-in silico virtual imaging clinical trial for regulatory evaluation (the VICTRE study).

scholarly journals Urban Air Quality Modeling Using Low-Cost Sensor Network and Data Assimilation in the Aburrá Valley, Colombia

Atmosphere ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 91
Author(s):  
Santiago Lopez-Restrepo ◽  
Andres Yarce ◽  
Nicolás Pinel ◽  
O.L. Quintero ◽  
Arjo Segers ◽  
...  
Keyword(s):  
Air Quality ◽  
Data Assimilation ◽  
Transport Model ◽  
Cost Model ◽  
Low Cost ◽  
Model Performance ◽  
Monitoring Network ◽  
Correlation Factor ◽  
Chemical Transport Model ◽  
High Quality

The use of low air quality networks has been increasing in recent years to study urban pollution dynamics. Here we show the evaluation of the operational Aburrá Valley’s low-cost network against the official monitoring network. The results show that the PM2.5 low-cost measurements are very close to those observed by the official network. Additionally, the low-cost allows a higher spatial representation of the concentrations across the valley. We integrate low-cost observations with the chemical transport model Long Term Ozone Simulation-European Operational Smog (LOTOS-EUROS) using data assimilation. Two different configurations of the low-cost network were assimilated: using the whole low-cost network (255 sensors), and a high-quality selection using just the sensors with a correlation factor greater than 0.8 with respect to the official network (115 sensors). The official stations were also assimilated to compare the more dense low-cost network’s impact on the model performance. Both simulations assimilating the low-cost model outperform the model without assimilation and assimilating the official network. The capability to issue warnings for pollution events is also improved by assimilating the low-cost network with respect to the other simulations. Finally, the simulation using the high-quality configuration has lower error values than using the complete low-cost network, showing that it is essential to consider the quality and location and not just the total number of sensors. Our results suggest that with the current advance in low-cost sensors, it is possible to improve model performance with low-cost network data assimilation.

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