scholarly journals Article Commentary: Drug Discovery Benefits from Venomous Clues

2010 ◽  
Vol 3 ◽  
pp. PRI.S6097
Author(s):  
Marc A. Williams
Keyword(s):  
Drug Discovery ◽  
Natural Resources ◽  
Cost Effective ◽  
Biologically Active ◽  
Discovery Research ◽  
Current Perspective ◽  
Drug Discovery Research ◽  
Drug Pipeline ◽  
Effective Drugs ◽  
Novel Drug

Pharmaceutical drug discovery is reliant on innovative research and development approaches that uncover novel agents that could service a drug pipeline. Development of novel drugs to combat human disease is largely dependent on the availability of safe and effective drugs, many of which are under development and evaluation–-the so-called “drug pipeline”. While the costs involved in novel drug discovery, research, development and clinical evaluation are quite significant, one approach that can prove both cost-effective and a viable source of bio-therapeutic agents involves bio-prospecting for therapeutically active compounds commonly found in natural resources including microorganisms, plants, invertebrates or reptiles. In a recent issue of Proteomic Insights, Hang Fai Kwok et al provide a historical and current perspective of proteomic and genomic approaches on lizard venoms that have allowed us to understand and appreciate not only this valuable resource of discovering biologically active molecules, but also to alert us to the need of conservation of such invaluable and beneficial natural resources.

scholarly journals Repurposing of the Open Access Malaria Box for Kinetoplastid Diseases Identifies Novel Active Scaffolds against Trypanosomatids

2015 ◽  
Vol 20 (5) ◽  
pp. 634-645 ◽  
Author(s):  
Marcel Kaiser ◽  
Louis Maes ◽  
Leela Pavan Tadoori ◽  
Thomas Spangenberg ◽  
Jean-Robert Ioset
Keyword(s):  
Drug Discovery ◽  
Leishmania Donovani ◽  
Human African Trypanosomiasis ◽  
Neglected Diseases ◽  
Discovery Research ◽  
Drug Discovery Research ◽  
Drug Pipeline ◽  
Malaria Box

Phenotypic screening had successfully been used for hit generation, especially in the field of neglected diseases, in which feeding the drug pipeline with new chemotypes remains a constant challenge. Here, we catalyze drug discovery research using a publicly available screening tool to boost drug discovery. The Malaria Box, assembled by the Medicines for Malaria Venture, is a structurally diverse set of 200 druglike and 200 probelike compounds distilled from more than 20,000 antimalarial hits from corporate and academic libraries. Repurposing such compounds has already identified new scaffolds against cryptosporidiosis and schistosomiasis. In addition to initiating new hit-to-lead activities, screening the Malaria Box against a plethora of other parasites would enable the community to better understand the similarities and differences between them. We describe the screening of the Malaria Box and triaging of the identified hits against kinetoplastids responsible for human African trypanosomiasis ( Trypanosoma brucei), Chagas disease ( Trypanosoma cruzi), and visceral leishmaniasis ( Leishmania donovani and Leishmania infantum). The in vitro and in vivo profiling of the most promising active compounds with respect to efficacy, toxicity, pharmacokinetics, and complementary druggable properties are presented and a collaborative model used as a way to accelerate the discovery process discussed.

scholarly journals Optimisation of Neuraminidase Expression for Use in Drug Discovery by Using HEK293-6E Cells

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1893
Author(s):  
Ashley C. Campbell ◽  
John J. Tanner ◽  
Kurt L. Krause
Keyword(s):  
Drug Discovery ◽  
Insect Cell ◽  
Human Cell Line ◽  
Human Infection ◽  
Mortality And Morbidity ◽  
Secretion Signal ◽  
Discovery Research ◽  
Drug Discovery Research ◽  
Method Of Production ◽  
Effective Drugs

Influenza virus is a highly contagious virus that causes significant human mortality and morbidity annually. The most effective drugs for treating influenza are the neuraminidase inhibitors, but resistance to these inhibitors has emerged, and additional drug discovery research on neuraminidase and other targets is needed. Traditional methods of neuraminidase production from embryonated eggs are cumbersome, while insect cell derived protein is less reflective of neuraminidase produced during human infection. Herein we describe a method for producing neuraminidase from a human cell line, HEK293-6E, and demonstrate the method by producing the neuraminidase from the 1918 H1N1 pandemic influenza strain. This method produced high levels of soluble neuraminidase expression (>3000 EU/mL), was enhanced by including a secretion signal from a viral chemokine binding protein, and does not require co-expression of additional proteins. The neuraminidase produced was of sufficient quantity and purity to support high resolution crystal structure determination. The structure solved using this protein conformed to the previously reported structure. Notably the glycosylation at three asparagine residues was superior in quality to that from insect cell derived neuraminidase. This method of production of neuraminidase should prove useful in further studies, such as the characterisation of inhibitor binding.

scholarly journals Modern Approaches in the Discovery and Development of Plant-Based Natural Products and Their Analogues as Potential Therapeutic Agents

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 349
Author(s):  
Asim Najmi ◽  
Sadique A. Javed ◽  
Mohammed Al Bratty ◽  
Hassan A. Alhazmi
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Natural Product ◽  
Therapeutic Agents ◽  
Throughput Capacity ◽  
Scientific Interest ◽  
Comprehensive Overview ◽  
Natural Sources ◽  
Discovery Research ◽  
Drug Discovery Research

Natural products represents an important source of new lead compounds in drug discovery research. Several drugs currently used as therapeutic agents have been developed from natural sources; plant sources are specifically important. In the past few decades, pharmaceutical companies demonstrated insignificant attention towards natural product drug discovery, mainly due to its intrinsic complexity. Recently, technological advancements greatly helped to address the challenges and resulted in the revived scientific interest in drug discovery from natural sources. This review provides a comprehensive overview of various approaches used in the selection, authentication, extraction/isolation, biological screening, and analogue development through the application of modern drug-development principles of plant-based natural products. Main focus is given to the bioactivity-guided fractionation approach along with associated challenges and major advancements. A brief outline of historical development in natural product drug discovery and a snapshot of the prominent natural drugs developed in the last few decades are also presented. The researcher’s opinions indicated that an integrated interdisciplinary approach utilizing technological advances is necessary for the successful development of natural products. These involve the application of efficient selection method, well-designed extraction/isolation procedure, advanced structure elucidation techniques, and bioassays with a high-throughput capacity to establish druggability and patentability of phyto-compounds. A number of modern approaches including molecular modeling, virtual screening, natural product library, and database mining are being used for improving natural product drug discovery research. Renewed scientific interest and recent research trends in natural product drug discovery clearly indicated that natural products will play important role in the future development of new therapeutic drugs and it is also anticipated that efficient application of new approaches will further improve the drug discovery campaign.

scholarly journals Induced Pluripotent HD Monkey Stem Cells Derived Neural Cells for Drug Discovery

2016 ◽  
Vol 22 (6) ◽  
pp. 696-705 ◽  
Author(s):  
Tanut Kunkanjanawan ◽  
Richard Carter ◽  
Kwan-Sung Ahn ◽  
Jinjing Yang ◽  
Rangsun Parnpai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Discovery ◽  
Trinucleotide Repeat ◽  
Yeast Cells ◽  
Neural Cells ◽  
Primate Model ◽  
Discovery Research ◽  
Drug Discovery Research ◽  
Induced Pluripotent

Huntington’s disease (HD) is a neurodegenerative disease caused by an expansion of CAG trinucleotide repeat (polyglutamine [polyQ]) in the huntingtin ( HTT) gene, which leads to the formation of mutant HTT (mHTT) protein aggregates. In the nervous system, an accumulation of mHTT protein results in glutamate-mediated excitotoxicity, proteosome instability, and apoptosis. Although HD pathogenesis has been extensively studied, effective treatment of HD has yet to be developed. Therapeutic discovery research in HD has been reported using yeast, cells derived from transgenic animal models and HD patients, and induced pluripotent stem cells from patients. A transgenic nonhuman primate model of HD (HD monkey) shows neuropathological, behavioral, and molecular changes similar to an HD patient. In addition, neural progenitor cells (NPCs) derived from HD monkeys can be maintained in culture and differentiated to neural cells with distinct HD cellular phenotypes including the formation of mHTT aggregates, intranuclear inclusions, and increased susceptibility to oxidative stress. Here, we evaluated the potential application of HD monkey NPCs and neural cells as an in vitro model for HD drug discovery research.

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