scholarly journals Antiviral Compounds for Blocking Arboviral Transmission in Mosquitoes

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 108
Author(s):  
Shengzhang Dong ◽  
George Dimopoulos
Keyword(s):  
High Throughput Screening ◽  
Mammalian Cells ◽  
Symbiotic Bacterium ◽  
Screening Methods ◽  
Human Pathogens ◽  
Inhibitory Effects ◽  
Antiviral Compounds ◽  
Mosquito Cells ◽  
Recent Emergence ◽  
Arboviral Transmission

Mosquito-borne arthropod-borne viruses (arboviruses) such as the dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) are important human pathogens that are responsible for significant global morbidity and mortality. The recent emergence and re-emergence of mosquito-borne viral diseases (MBVDs) highlight the urgent need for safe and effective vaccines, therapeutics, and vector-control approaches to prevent MBVD outbreaks. In nature, arboviruses circulate between vertebrate hosts and arthropod vectors; therefore, disrupting the virus lifecycle in mosquitoes is a major approach for combating MBVDs. Several strategies were proposed to render mosquitoes that are refractory to arboviral infection, for example, those involving the generation of genetically modified mosquitoes or infection with the symbiotic bacterium Wolbachia. Due to the recent development of high-throughput screening methods, an increasing number of drugs with inhibitory effects on mosquito-borne arboviruses in mammalian cells were identified. These antivirals are useful resources that can impede the circulation of arboviruses between arthropods and humans by either rendering viruses more vulnerable in humans or suppressing viral infection by reducing the expression of host factors in mosquitoes. In this review, we summarize recent advances in small-molecule antiarboviral drugs in mammalian and mosquito cells, and discuss how to use these antivirals to block the transmission of MBVDs.

High throughput screening methods for freeze-drying of fungi and mammalian cells

Cryobiology ◽  
2016 ◽  
Vol 73 (3) ◽  
pp. 425
Author(s):  
P. Kilbride ◽  
E. Thompson ◽  
M. Ryan ◽  
K. Mahbubani ◽  
B. Luke ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Mammalian Cells ◽  
Freeze Drying ◽  
Screening Methods

scholarly journals Diversity, evolution and medical applications of insect antimicrobial peptides

2016 ◽  
Vol 371 (1695) ◽  
pp. 20150290 ◽  
Author(s):  
Eleftherios Mylonakis ◽  
Lars Podsiadlowski ◽  
Maged Muhammed ◽  
Andreas Vilcinskas
Keyword(s):  
Antimicrobial Peptides ◽  
High Throughput Screening ◽  
Rational Design ◽  
Evolutionary Ecology ◽  
Multidrug Resistant ◽  
Screening Methods ◽  
Medical Applications ◽  
Human Pathogens ◽  
Acinetobacter Baumanii ◽  
Multidrug Resistant Pathogens

Antimicrobial peptides (AMPs) are short proteins with antimicrobial activity. A large portion of known AMPs originate from insects, and the number and diversity of these molecules in different species varies considerably. Insect AMPs represent a potential source of alternative antibiotics to address the limitation of current antibiotics, which has been caused by the emergence and spread of multidrug-resistant pathogens. To get more insight into AMPs, we investigated the diversity and evolution of insect AMPs by mapping their phylogenetic distribution, allowing us to predict the evolutionary origins of selected AMP families and to identify evolutionarily conserved and taxon-specific families. Furthermore, we highlight the use of the nematode Caenorhabditis elegans as a whole-animal model in high-throughput screening methods to identify AMPs with efficacy against human pathogens, including Acinetobacter baumanii and methicillin-resistant Staphylococcus aureus . We also discuss the potential medical applications of AMPs, including their use as alternatives for conventional antibiotics in ectopic therapies, their combined use with antibiotics to restore the susceptibility of multidrug-resistant pathogens, and their use as templates for the rational design of peptidomimetic drugs that overcome the disadvantages of therapeutic peptides. The article is part of the themed issue ‘Evolutionary ecology of arthropod antimicrobial peptides’.

From Classical to High Throughput Screening Methods for Feruloyl Esterases: A Review

2016 ◽  
Vol 19 (8) ◽  
pp. 616-626 ◽  
Author(s):  
Lorena Ramírez-Velasco ◽  
Mariana Armendáriz-Ruiz ◽  
Jorge Alberto Rodríguez-González ◽  
Marcelo Müller-Santos ◽  
Ali Asaff-Torres ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Screening Methods ◽  
Feruloyl Esterases

scholarly journals Discovery of SARS-CoV-2-E channel inhibitors as antiviral candidates

2021 ◽  
Author(s):  
Yi Wang ◽  
Sui Fang ◽  
Yan Wu ◽  
Xi Cheng ◽  
Lei-ke Zhang ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Antiviral Drug ◽  
Binding Pocket ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Cell Protection ◽  
Host Cell Death ◽  
A Cell ◽  
Protection Activity ◽  
Molecular Modeling And Docking

AbstractLack of efficiency has been a major problem shared by all currently developed anti-SARS-CoV-2 therapies. Our previous study shows that SARS-CoV-2 structural envelope (2-E) protein forms a type of cation channel, and heterogeneously expression of 2-E channels causes host cell death. In this study we developed a cell-based high throughput screening (HTS) assay and used it to discover inhibitors against 2-E channels. Among 4376 compounds tested, 34 hits with cell protection activity were found. Followed by an anti-viral analysis, 15 compounds which could inhibit SARS-CoV-2 replication were identified. In electrophysiological experiments, three representatives showing inhibitory effect on 2-E channels were chosen for further characterization. Among them, proanthocyanidins directly bound to 2-E channel with binding affinity (KD) of 22.14 μM in surface plasmon resonance assay. Molecular modeling and docking analysis revealed that proanthocyanidins inserted into the pore of 2-E N-terminal vestibule acting as a channel blocker. Consistently, mutations of Glu 8 and Asn 15, two residues lining the proposed binding pocket, abolished the inhibitory effects of proanthocyanidins. The natural product proanthocyanidins are widely used as cosmetic, suggesting a potential of proanthocyanidins as disinfectant for external use. This study further demonstrates that 2-E channel is an effective antiviral drug target and provides a potential antiviral candidate against SARS-CoV-2.

scholarly journals Inhibitory effects of selected antiviral compounds on human hepatitis B virus DNA synthesis.

1991 ◽  
Vol 35 (2) ◽  
pp. 394-397 ◽  
Author(s):  
T Yokota ◽  
S Mochizuki ◽  
K Konno ◽  
S Mori ◽  
S Shigeta ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Dna Synthesis ◽  
Inhibitory Effects ◽  
Hepatitis B Virus Dna ◽  
Antiviral Compounds ◽  
Human Hepatitis ◽  
B Virus

scholarly journals Primary and Secondary Drug Screening Assays for Friedreich Ataxia

2011 ◽  
Vol 17 (3) ◽  
pp. 303-313 ◽  
Author(s):  
M. Grazia Cotticelli ◽  
Lynn Rasmussen ◽  
Nicole L. Kushner ◽  
Sara McKellip ◽  
Melinda Ingrum Sosa ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
High Throughput Screening ◽  
Mammalian Cells ◽  
Friedreich Ataxia ◽  
Krebs Cycle ◽  
C2c12 Cells ◽  
Transport Chain ◽  
Screening Assays ◽  
Yeast Mutants

Friedreich ataxia (FRDA) is an autosomal recessive neuro- and cardiodegenerative disorder for which there are no proven effective treatments. FRDA is caused by decreased expression and/or function of the protein frataxin. Frataxin chaperones iron in the mitochondrial matrix for the assembly of iron–sulfur clusters (ISCs), which are prosthetic groups critical for the function of the Krebs cycle and the mitochondrial electron transport chain (ETC). Decreased expression of frataxin or the yeast frataxin orthologue, Yfh1p, is associated with decreased ISC assembly, mitochondrial iron accumulation, and increased oxidative stress, all of which contribute to mitochondrial dysfunction. Using yeast depleted of Yfh1p, a high-throughput screening (HTS) assay was developed in which mitochondrial function was monitored by reduction of the tetrazolium dye WST-1 in a growth medium with a respiration-only carbon source. Of 101 200 compounds screened, 302 were identified that effectively rescue mitochondrial function. To confirm activities in mammalian cells and begin understanding mechanisms of action, secondary screening assays were developed using murine C2C12 cells and yeast mutants lacking specific complexes of the ETC, respectively. The compounds identified in this study have potential relevance for other neurodegenerative disorders associated with mitochondrial dysfunction, such as Parkinson disease.

scholarly journals Optimization Procedure for Small Interfering RNA Transfection in a 384-Well Format

2007 ◽  
Vol 12 (4) ◽  
pp. 546-559 ◽  
Author(s):  
Jason Borawski ◽  
Alicia Lindeman ◽  
Frank Buxton ◽  
Mark Labow ◽  
L. Alex Gaither
Keyword(s):  
High Throughput Screening ◽  
Mammalian Cells ◽  
Small Interfering Rna ◽  
Dna Analysis ◽  
Lentiviral Vector ◽  
Mrna Levels ◽  
Sirna Transfection ◽  
Rna Transfection ◽  
Well Assay ◽  
Interfering Rna

High-throughput screening of RNAi libraries has become an essential part of functional analysis in academic and industrial settings. The transition of a cell-based RNAi assay into a 384-well format requires several optimization steps to ensure the phenotype being screened is appropriately measured and that the signal-to-background ratio is above a certain quantifiable threshold. Methods currently used to assess small interfering RNA (siRNA) efficacy after transfection, including quantitative PCR or branch DNA analysis, face several technical limitations preventing the accurate measurement of mRNA levels in a 384-well format. To overcome these difficulties, the authors developed an approach using a viral-based transfection system that measures siRNA efficacy in a standardized 384-well assay. This method allows measurement of siRNA activity in a phenotypically neutral manner by quantifying the knockdown of an exogenous luciferase gene delivered by a lentiviral vector. In this assay, the efficacy of a luciferase siRNA is compared to a negative control siRNA across many distinct assay parameters including cell type, cell number, lipid type, lipid volume, time of the assay, and concentration of siRNA. Once the siRNA transfection is optimized as a 384-well luciferase knockdown, the biologically relevant phenotypic analysis can proceed using the best siRNA transfection conditions. This approach provides a key technology for 384-well assay development when direct measurement of mRNA knockdown is not possible. It also allows for direct comparison of siRNA activity across cell lines from almost any mammalian species. Defining optimal conditions for siRNA delivery into mammalian cells will greatly increase the speed and quality of large-scale siRNA screening campaigns. ( Journal of Biomolecular Screening 2007:546-559)

scholarly journals Advances in Antarctic Research for Antimicrobial Discovery: A Comprehensive Narrative Review of Bacteria from Antarctic Environments as Potential Sources of Novel Antibiotic Compounds Against Human Pathogens and Microorganisms of Industrial Importance

Antibiotics ◽  
2018 ◽  
Vol 7 (4) ◽  
pp. 90 ◽  
Author(s):  
Kattia Núñez-Montero ◽  
Leticia Barrientos
Keyword(s):  
Public Health Problem ◽  
Narrative Review ◽  
Bioactive Molecules ◽  
Resistant Bacteria ◽  
Natural Environments ◽  
Antimicrobial Compounds ◽  
Human Pathogens ◽  
Bacterial Strains ◽  
Antarctic Bacteria ◽  
Recent Emergence

The recent emergence of antibiotic-resistant bacteria has become a critical public health problem. It is also a concern for industries, since multidrug-resistant microorganisms affect the production of many agricultural and food products of economic importance. Therefore, discovering new antibiotics is crucial for controlling pathogens in both clinical and industrial spheres. Most antibiotics have resulted from bioprospecting in natural environments. Today, however, the chances of making novel discoveries of bioactive molecules from various well-known sources have dramatically diminished. Consequently, unexplored and unique environments have become more likely avenues for discovering novel antimicrobial metabolites from bacteria. Due to their extreme polar environment, Antarctic bacteria in particular have been reported as a potential source for new antimicrobial compounds. We conducted a narrative review of the literature about findings relating to the production of antimicrobial compounds by Antarctic bacteria, showing how bacterial adaptation to extreme Antarctic conditions confers the ability to produce these compounds. We highlighted the diversity of antibiotic-producing Antarctic microorganisms, including the phyla Proteobacteria, Actinobacteria, Cyanobacteria, Firmicutes, and Bacteroidetes, which has led to the identification of new antibiotic molecules and supports the belief that research on Antarctic bacterial strains has important potential for biotechnology applications, while providing a better understanding of polar ecosystems.

scholarly journals Practical Model Selection for Prospective Virtual Screening

2018 ◽  
Author(s):  
Shengchao Liu ◽  
Moayad Alnammi ◽  
Spencer S. Ericksen ◽  
Andrew F. Voter ◽  
Gene E. Ananiev ◽  
...  
Keyword(s):  
Random Forest ◽  
Virtual Screening ◽  
Protein Interactions ◽  
High Throughput Screening ◽  
Screening Methods ◽  
Protein Protein Interactions ◽  
Screening Algorithm ◽  
Screening Performance ◽  
Wide Range ◽  
Public Datasets

AbstractVirtual (computational) high-throughput screening provides a strategy for prioritizing compounds for experimental screens, but the choice of virtual screening algorithm depends on the dataset and evaluation strategy. We consider a wide range of ligand-based machine learning and docking-based approaches for virtual screening on two protein-protein interactions, PriA-SSB and RMI-FANCM, and present a strategy for choosing which algorithm is best for prospective compound prioritization. Our workflow identifies a random forest as the best algorithm for these targets over more sophisticated neural network-based models. The top 250 predictions from our selected random forest recover 37 of the 54 active compounds from a library of 22,434 new molecules assayed on PriA-SSB. We show that virtual screening methods that perform well in public datasets and synthetic benchmarks, like multi-task neural networks, may not always translate to prospective screening performance on a specific assay of interest.

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