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.

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.

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.

scholarly journals Lipid-Based Nanoparticles in the Clinic and Clinical Trials: From Cancer Nanomedicine to COVID-19 Vaccines

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 359
Author(s):  
Thai Thanh Hoang Thi ◽  
Estelle J. A. Suys ◽  
Jung Seok Lee ◽  
Dai Hai Nguyen ◽  
Ki Dong Park ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Clinical Trials ◽  
Physicochemical Properties ◽  
Solid Lipid Nanoparticles ◽  
Drug Delivery Systems ◽  
Lipid Nanoparticles ◽  
Therapeutic Vaccines ◽  
Cancer Nanomedicine ◽  
Fundamental Research ◽  
Further Development

COVID-19 vaccines have been developed with unprecedented speed which would not have been possible without decades of fundamental research on delivery nanotechnology. Lipid-based nanoparticles have played a pivotal role in the successes of COVID-19 vaccines and many other nanomedicines, such as Doxil® and Onpattro®, and have therefore been considered as the frontrunner in nanoscale drug delivery systems. In this review, we aim to highlight the progress in the development of these lipid nanoparticles for various applications, ranging from cancer nanomedicines to COVID-19 vaccines. The lipid-based nanoparticles discussed in this review are liposomes, niosomes, transfersomes, solid lipid nanoparticles, and nanostructured lipid carriers. We particularly focus on the innovations that have obtained regulatory approval or that are in clinical trials. We also discuss the physicochemical properties required for specific applications, highlight the differences in requirements for the delivery of different cargos, and introduce current challenges that need further development. This review serves as a useful guideline for designing new lipid nanoparticles for both preventative and therapeutic vaccines including immunotherapies.

Clinical Trials and Machine Learning: Regulatory Approach Review

2021 ◽  
Vol 16 ◽  
Author(s):  
Diego Alejandro Dri ◽  
Maurizio Massella ◽  
Donatella Gramaglia ◽  
Carlotta Marianecci ◽  
Sandra Petraglia
Keyword(s):  
Artificial Intelligence ◽  
Machine Learning ◽  
Clinical Trials ◽  
Patient Safety ◽  
Drug Discovery ◽  
Clinical Applications ◽  
Clinical Development ◽  
Regulatory Approach ◽  
National Competent Authorities ◽  
Review Current

: Machine Learning, a fast-growing technology, is an application of Artificial Intelligence that has significantly contributed to drug discovery and clinical development. In the last few years, the number of clinical applications based on Machine Learning has constantly been growing. Moreover, it is now also impacting National Competent Authorities during the assessment of most recently submitted Clinical Trials that are designed, managed, or generating data deriving from the use of Machine Learning or Artificial Intelligence technologies. We review current information available on the regulatory approach to Clinical Trials and Machine Learning. We also provide inputs for further reasoning and potential indications, including six actionable proposals for regulators to proactively drive the upcoming evolution of Clinical Trials within a strong regulatory framework, focusing on patient safety, health protection, and fostering immediate access to effective treatments.

scholarly journals Phase I and phase II clinical trials in sarcoma: Implications for drug discovery and development

2019 ◽  
Vol 8 (2) ◽  
pp. 585-592 ◽  
Author(s):  
Daniel Y. Lee ◽  
Arthur P. Staddon ◽  
Jacob E. Shabason ◽  
Ronnie Sebro
Keyword(s):  
Clinical Trials ◽  
Drug Discovery ◽  
Phase I ◽  
Phase Ii ◽  
Drug Discovery And Development ◽  
Phase Ii Clinical Trials

Structural biology approaches to antibacterial drug discovery

2007 ◽  
Vol 2 (8) ◽  
pp. 1085-1101 ◽  
Author(s):  
Tod P Holler ◽  
Artem G Evdokimov ◽  
Lakshmi Narasimhan
Keyword(s):  
Drug Discovery ◽  
Structural Biology ◽  
Antibacterial Drug

scholarly journals Structural biology in antiviral drug discovery

2016 ◽  
Vol 30 ◽  
pp. 116-130 ◽  
Author(s):  
Marcella Bassetto ◽  
Alberto Massarotti ◽  
Antonio Coluccia ◽  
Andrea Brancale
Keyword(s):  
Drug Discovery ◽  
Structural Biology ◽  
Antiviral Drug

scholarly journals Variants in Host Viral Replication Cycle Genes Are Associated With Heterosexual HIV-1 Acquisition in Africans

2014 ◽  
Vol 66 (2) ◽  
pp. 127-134 ◽  
Author(s):  
Abigail W. Bigham ◽  
Romel D. Mackelprang ◽  
Connie Celum ◽  
Guy De Bruyn ◽  
Kristin Beima-Sofie ◽  
...  
Keyword(s):  
Viral Replication ◽  
Replication Cycle ◽  
Hiv 1
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