scholarly journals Open drug discovery for the Zika virus

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 150 ◽  
Author(s):  
Sean Ekins ◽  
Daniel Mietchen ◽  
Megan Coffee ◽  
Thomas P Stratton ◽  
Joel S Freundlich ◽  
...  

The Zika virus (ZIKV) outbreak in the Americas has caused global concern that we may be on the brink of a healthcare crisis. The lack of research on ZIKV in the over 60 years that we have known about it has left us with little in the way of starting points for drug discovery. Our response can build on previous efforts with virus outbreaks and lean heavily on work done on other flaviviruses such as dengue virus. We provide some suggestions of what might be possible and propose an open drug discovery effort that mobilizes global science efforts and provides leadership, which thus far has been lacking. We also provide a listing of potential resources and molecules that could be prioritized for testing as in vitro assays for ZIKV are developed. We propose also that in order to incentivize drug discovery, a neglected disease priority review voucher should be available to those who successfully develop an FDA approved treatment. Learning from the response to the ZIKV, the approaches to drug discovery used and the success and failures will be critical for future infectious disease outbreaks.

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 110
Author(s):  
Nayara Sousa da Silva ◽  
Nathália Kelly Araújo ◽  
Alessandra Daniele-Silva ◽  
Johny Wysllas de Freitas Oliveira ◽  
Júlia Maria de Medeiros ◽  
...  

The global rise of infectious disease outbreaks and the progression of microbial resistance reinforce the importance of researching new biomolecules. Obtained from the hydrolysis of chitosan, chitooligosaccharides (COSs) have demonstrated several biological properties, including antimicrobial, and greater advantage over chitosan due to their higher solubility and lower viscosity. Despite the evidence of the biotechnological potential of COSs, their effects on trypanosomatids are still scarce. The objectives of this study were the enzymatic production, characterization, and in vitro evaluation of the cytotoxic, antibacterial, antifungal, and antiparasitic effects of COSs. NMR and mass spectrometry analyses indicated the presence of a mixture with 81% deacetylated COS and acetylated hexamers. COSs demonstrated no evidence of cytotoxicity upon 2 mg/mL. In addition, COSs showed interesting activity against bacteria and yeasts and a time-dependent parasitic inhibition. Scanning electron microscopy images indicated a parasite aggregation ability of COSs. Thus, the broad biological effect of COSs makes them a promising molecule for the biomedical industry.


2016 ◽  
Vol 2 (9) ◽  
pp. e1600025 ◽  
Author(s):  
Amirali Aghazadeh ◽  
Adam Y. Lin ◽  
Mona A. Sheikh ◽  
Allen L. Chen ◽  
Lisa M. Atkins ◽  
...  

Early identification of pathogens is essential for limiting development of therapy-resistant pathogens and mitigating infectious disease outbreaks. Most bacterial detection schemes use target-specific probes to differentiate pathogen species, creating time and cost inefficiencies in identifying newly discovered organisms. We present a novel universal microbial diagnostics (UMD) platform to screen for microbial organisms in an infectious sample, using a small number of random DNA probes that are agnostic to the target DNA sequences. Our platform leverages the theory of sparse signal recovery (compressive sensing) to identify the composition of a microbial sample that potentially contains novel or mutant species. We validated the UMD platform in vitro using five random probes to recover 11 pathogenic bacteria. We further demonstrated in silico that UMD can be generalized to screen for common human pathogens in different taxonomy levels. UMD’s unorthodox sensing approach opens the door to more efficient and universal molecular diagnostics.


Author(s):  
Antonia Molloy ◽  
James Harrison ◽  
John McGrath ◽  
Zachary Owen ◽  
Clive Smith ◽  
...  

Tuberculosis (TB) remains a global healthcare crisis with an estimated 10 million new cases and 1.4 million deaths per year TB is caused by infection with the major human pathogen Mycobacte-rium tuberculosis, which is difficult to rapidly diagnose and treat. There is an urgent need for new methods of diagnosis, sufficient in vitro models which capably mimic all physiological condi-tions of the infection, and high-throughput drug screening platforms. Microfluidic-based tech-niques provide single-cell analysis which reduces experimental time, the cost of reagents, and have been extremely useful for gaining insight into monitoring microorganisms. This review out-lines the field of microfluidics and discusses the use of this novel technique so far in M. tuberculo-sis diagnostics, research methods, and drug discovery platforms. The practices of microfluidics have promising future applications for diagnosing and treating TB.


2021 ◽  
Vol 9 (11) ◽  
pp. 2330
Author(s):  
Antonia Molloy ◽  
James Harrison ◽  
John S. McGrath ◽  
Zachary Owen ◽  
Clive Smith ◽  
...  

Tuberculosis (TB) remains a global healthcare crisis, with an estimated 5.8 million new cases and 1.5 million deaths in 2020. TB is caused by infection with the major human pathogen Mycobacterium tuberculosis, which is difficult to rapidly diagnose and treat. There is an urgent need for new methods of diagnosis, sufficient in vitro models that capably mimic all physiological conditions of the infection, and high-throughput drug screening platforms. Microfluidic-based techniques provide single-cell analysis which reduces experimental time and the cost of reagents, and have been extremely useful for gaining insight into monitoring microorganisms. This review outlines the field of microfluidics and discusses the use of this novel technique so far in M. tuberculosis diagnostics, research methods, and drug discovery platforms. The practices of microfluidics have promising future applications for diagnosing and treating TB.


2016 ◽  
Vol 85 (2) ◽  
pp. 63-65
Author(s):  
Matt Douglas-Vail ◽  
Hong Yu (Andrew) Su

Before 2015, few people outside the infectious disease community had heard of Zika virus. However, this virus is now the centre of global conscience. Pictures of newborns with microcephaly have been widely circulated and misinformation abounded. This piece explores and examines the evolution of infectious disease outbreaks, in addition to the historical public health responses. This investigation serves to garner lessons which can be applied to the current Zika outbreak. The virus’ role as a pathogen is introduced, and current public health responses and their impacts are also examined. Finally, we posit what Canada’s role should be in the midst of this outbreak.


2019 ◽  
Vol 13 (5-6) ◽  
pp. 989-994 ◽  
Author(s):  
Leah S. Fischer ◽  
Gordon Mansergh ◽  
Jonathan Lynch ◽  
Scott Santibanez

ABSTRACTOutbreaks of emerging infectious disease are a constant threat. In the last 10 years, there have been outbreaks of 2009 influenza A (H1N1), Ebola virus disease, and Zika virus. Stigma associated with infectious disease can be a barrier to adopting healthy behaviors, leading to more severe health problems, ongoing disease transmission, and difficulty controlling infectious disease outbreaks. Much has been learned about infectious disease and stigma in the context of nearly 4 decades of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome pandemic. In this paper, we define stigma, discuss its relevance to infectious disease outbreaks, including how individuals and communities can be affected. Adapting lessons learned from the rich literature on HIV-related stigma, we propose a strategy for reducing stigma during infectious disease outbreaks such as Ebola virus disease and Zika virus. The implementation of brief, practical strategies such as the ones proposed here might help reduce stigma and facilitate more effective control of emerging infectious diseases.


2019 ◽  
Vol 22 (8) ◽  
pp. 509-520
Author(s):  
Cauê B. Scarim ◽  
Chung M. Chin

Background: In recent years, there has been an improvement in the in vitro and in vivo methodology for the screening of anti-chagasic compounds. Millions of compounds can now have their activity evaluated (in large compound libraries) by means of high throughput in vitro screening assays. Objective: Current approaches to drug discovery for Chagas disease. Method: This review article examines the contribution of these methodological advances in medicinal chemistry in the last four years, focusing on Trypanosoma cruzi infection, obtained from the PubMed, Web of Science, and Scopus databases. Results: Here, we have shown that the promise is increasing each year for more lead compounds for the development of a new drug against Chagas disease. Conclusion: There is increased optimism among those working with the objective to find new drug candidates for optimal treatments against Chagas disease.


Author(s):  
Morganna C. Lima ◽  
Elisa A. N. Azevedo ◽  
Clarice N. L. de Morais ◽  
Larissa I. O. de Sousa ◽  
Bruno M. Carvalho ◽  
...  

Background: Zika virus is an emerging arbovirus of global importance. ZIKV infection is associated with a range of neurological complications such as the Congenital Zika Syndrome and Guillain Barré Syndrome. Despite the magnitude of recent outbreaks, there is no specific therapy to prevent or to alleviate disease pathology. Objective: To investigate the role of P-MAPA immunomodulator in Zika-infected THP-1 cells. Methods: THP-1 cells were subjected at Zika virus infection (Multiplicity of Infection = 0.5) followed by treatment with P-MAPA for until 96 hours post-infection. After that, the cell death was analyzed by annexin+/ PI+ and caspase 3/ 7+ staining by flow cytometry. In addition, the virus replication and cell proliferation were accessed by RT-qPCR and Ki67 staining, respectively. Results: We demonstrate that P-MAPA in vitro treatment significantly reduces Zika virus-induced cell death and caspase-3/7 activation on THP-1 infected cells, albeit it has no role in virus replication and cell proliferation. Conclusions: Our study reveals that P-MAPA seems to be a satisfactory alternative to inhibits the effects of Zika virus infection in mammalian cells.


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