scholarly journals In-Silico Identification of the Best Compound Against Leishmania infantum: High Throughput Screening of All FDA Approved Drugs

2019 ◽  
Vol 43 (4) ◽  
pp. 158-164
Author(s):  
Jasem Saki ◽  
Farnoush Shadnoush ◽  
Reza Arjmand ◽  
Fakher Rahim
Keyword(s):  
High Throughput ◽  
In Silico ◽  
Leishmania Infantum ◽  
High Throughput Screening ◽  
In Silico Identification ◽  
Approved Drugs ◽  
Fda Approved Drugs

Abstract 100: High-throughput Screening of FDA-approved Drugs Identifies Novel Inhibitors of Macropinocytosis

2018 ◽  
Vol 38 (Suppl_1) ◽  
Author(s):  
Hui-Ping Lin ◽  
Pushpankur Ghoshal ◽  
Bhupesh Singla ◽  
Jessica L Faulkner ◽  
Mary C Shaw ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Approved Drugs ◽  
Fda Approved Drugs

scholarly journals High-throughput screening of FDA-approved drugs using oxygen biosensor plates reveals secondary mitofunctional effects

Mitochondrion ◽  
2014 ◽  
Vol 17 ◽  
pp. 116-125 ◽  
Author(s):  
Sunil Sahdeo ◽  
Alexey Tomilov ◽  
Kelly Komachi ◽  
Christine Iwahashi ◽  
Sandipan Datta ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Approved Drugs ◽  
Fda Approved Drugs

scholarly journals A High-Throughput Screening Approach To Repurpose FDA-Approved Drugs for Bactericidal Applications againstStaphylococcus aureusSmall-Colony Variants

mSphere ◽  
2018 ◽  
Vol 3 (5) ◽  
Author(s):  
Ryan P. Trombetta ◽  
Paul M. Dunman ◽  
Edward M. Schwarz ◽  
Stephen L. Kates ◽  
Hani A. Awad
Keyword(s):  
High Throughput ◽  
Bactericidal Activity ◽  
High Throughput Screening ◽  
Drug Repurposing ◽  
Growth Patterns ◽  
Content Type ◽  
Airway Infections ◽  
Approved Drugs ◽  
Conventional Antibiotics ◽  
Fda Approved Drugs

ABSTRACTDrug repurposing offers an expedited and economical route to develop new clinical therapeutics in comparison to traditional drug development. Growth-based high-throughput screening is concomitant with drug repurposing and enables rapid identification of new therapeutic uses for investigated drugs; however, this traditional method is not compatible with microorganisms with abnormal growth patterns such asStaphylococcus aureussmall-colony variants (SCV). SCV subpopulations are auxotrophic for key compounds in biosynthetic pathways, which result in low growth rate. SCV formation is also associated with reduced antibiotic susceptibility, and the SCV’s ability to revert to the normal cell growth state is thought to contribute to recurrence ofS. aureusinfections. Thus, there is a critical need to identify antimicrobial agents that are potent against SCV in order to effectively treat chronic infections. Accordingly, here we describe adapting an adenylate kinase (AK)-based cell death reporter assay to identify members of a Food and Drug Administration (FDA)-approved drug library that display bactericidal activity againstS. aureusSCV. Four library members, daunorubicin, ketoconazole, rifapentine, and sitafloxacin, exhibited potent SCV bactericidal activity against a stableS. aureusSCV. Further investigation showed that sitafloxacin was potent against methicillin-susceptible and -resistantS. aureus, as well asS. aureuswithin an established biofilm. Taken together, these results demonstrate the ability to use the AK assay to screen small-molecule libraries for SCV bactericidal agents and highlight the therapeutic potential of sitafloxacin to be repurposed to treat chronicS. aureusinfections associated with SCV and/or biofilm growth states.IMPORTANCEConventional antibiotics fail to successfully treat chronic osteomyelitis, endocarditis, and device-related and airway infections. These recurring infections are associated with the emergence of SCV, which are recalcitrant to conventional antibiotics. Studies have investigated antibiotic therapies to treat SCV-related infections but have had little success, emphasizing the need to identify novel antimicrobial drugs. However, drug discovery is a costly and time-consuming process. An alternative strategy is drug repurposing, which could identify FDA-approved and well-characterized drugs that could have off-label utility in treating SCV. In this study, we adapted a high-throughput AK-based assay to identify 4 FDA-approved drugs, daunorubicin, ketoconazole, rifapentine, and sitafloxacin, which display antimicrobial activity againstS. aureusSCV, suggesting an avenue for drug repurposing in order to effectively treat SCV-related infections. Additionally, this screening paradigm can easily be adapted for other drug/chemical libraries to identify compounds bactericidal against SCV.

In silico identification of novel kinase inhibitors targeting wild-type and T315I mutant ABL1 from FDA-approved drugs

2014 ◽  
Vol 10 (6) ◽  
pp. 1524 ◽  
Author(s):  
Huai-long Xu ◽  
Zi-jie Wang ◽  
Xiao-meng Liang ◽  
Xin Li ◽  
Zheng Shi ◽  
...  
Keyword(s):  
In Silico ◽  
Kinase Inhibitors ◽  
Wild Type ◽  
In Silico Identification ◽  
Approved Drugs ◽  
Fda Approved Drugs

In silico identification and high throughput screening of antigenic proteins as candidates for a Mannheimia haemolytica vaccine

2018 ◽  
Vol 195 ◽  
pp. 19-24 ◽  
Author(s):  
Cassidy L. Klima ◽  
Rahat Zaheer ◽  
Shaun R. Cook ◽  
Jay Rasmussen ◽  
Trevor W. Alexander ◽  
...  
Keyword(s):  
High Throughput ◽  
In Silico ◽  
High Throughput Screening ◽  
Mannheimia Haemolytica ◽  
Antigenic Proteins ◽  
In Silico Identification

scholarly journals New mechanisms of radioiodide uptake revealed via a novel high throughput drug screening approach in thyroid cancer

2020 ◽  
Author(s):  
Martin L. Read ◽  
Katie Brookes ◽  
Caitlin E.M. Thornton ◽  
Alice Fletcher ◽  
Mohammed Alshahrani ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
High Throughput ◽  
High Throughput Screening ◽  
Fluorescent Protein ◽  
Yellow Fluorescent Protein ◽  
Cancer Genes ◽  
Iodide Uptake ◽  
Approved Drugs ◽  
The Impact ◽  
Fda Approved Drugs

ABSTRACTNew combinatorial drug strategies are urgently needed to improve radioiodide (RAI) uptake and efficiently ablate thyroid cancer cells, thereby addressing recurrent and metastatic disease. Cellular iodide uptake is accomplished solely by the sodium iodide symporter (NIS), but the complexity of NIS functional regulation and a lack of amenable high-throughput screening assays has impeded progress. We utilised mutated yellow fluorescent protein (YFP) as a surrogate biosensor of intracellular iodide for ∼1200 FDA-approved drugs, allowing us to appraise the impact of 73 leading compounds at 10 doses on 125I uptake in thyroid cancer cell lines. Subsequent mechanistic analysis suggests three predominant modes of drug action: Firstly, a number of drugs inhibited specific regulation of NIS function by the protein VCP. Secondly, some drugs enhanced transcriptional or post-transcriptional regulation of NIS expression. Thirdly, several drugs strongly implicated proteasomal degradation and the unfolded protein response in the cellular processing of NIS. Exploiting these mechanistic insights, multiple compounds gave striking increases in radioiodide uptake when combined with the drug SAHA. Importantly, our new drug combination strategies were also effective in human primary thyrocytes, suggesting they target endogenous NIS physiology. In patients with papillary thyroid cancer, genes involved in proteostasis were remarkably altered and predicted significantly worse outcome, but only in those patients who received RAI therapy. Collectively, we therefore propose a new model of intracellular NIS processing, and identify key nodes which may now be druggable in patients with aggressive thyroid cancer.SUMMARYOur data identify FDA-approved drugs that enhance radioiodide uptake outside of the canonical pathways of NIS processing, leading to a new mechanistic understanding of endogenous NIS function which is subverted in cancer.

scholarly journals In-silico identification of natural antiviral drug against SARS-CoV-2 and comparison with potential FDA approved drug targets

2020 ◽  
Vol 3 (4) ◽  
pp. 1-11
Author(s):  
SARRA AKERMI ◽  
Neha Lohar ◽  
Subrata Sinha ◽  
Surabhi Johari ◽  
Sunil Jayant ◽  
...  
Keyword(s):  
Free Energy ◽  
In Silico ◽  
High Throughput Screening ◽  
Drug Targets ◽  
Antiviral Drug ◽  
Spike Protein ◽  
Plant Metabolites ◽  
Secondary Plant Metabolites ◽  
Approved Drugs ◽  
Fda Approved Drugs

Antimalarial drugs Chloroquine and Hydroxychloroquine have garnered most attention recently as a successful remedy for COVID19. However, the use of these drugs is still questionable due to its undetermined efficacy and side effects. The present study utilizes in-silico high throughput screening of FDA approved antiviral compounds and secondary plant metabolites against spike protein of novel coronavirus (SARS-CoV-2). This target was chosen because it is instrumental in entry of virus into human cells. It is observed that the plant compound Tocopheryl-curcumin has more affinity for spike protein of SARS-CoV-2 in comparison to the majority of FDA approved drugs. Tocopheryl-curcumin binds with the binding site of RBD domain of spike protein (6VSB, chain A) with free energy (∆G) of binding of -11.20 kcal/mol and makes strong hydrogen bonds with amino acid residues of S366, V367, L368, S373, and K529. Among the FDA approved drugs, Pibrentasvir obtains top rank with free energy (∆G) of binding of -9.69 kcal/mol. whereas; surprisingly Chloroquine (-6.87 kcal/mol) and Hydroxychloroquine (-7.24 kcal/mol) ranked lower in our docking study. The toxicity prediction by VEGA predicts that tocopheryl-curcumin shows no toxicity as compared to FDA approved drugs. Therefore, we infer that the plant-based tocopheryl-curcumin could be considered as potential and safer drug against COVID 19 disease as compared to chemical based drugs.

scholarly journals Development of a High-Throughput Screening Assay to Identify Inhibitors of the SARS-CoV-2 Guanine-N7-Methyltransferase Using RapidFire Mass Spectrometry

2021 ◽  
pp. 247255522110006
Author(s):  
Lesley-Anne Pearson ◽  
Charlotte J. Green ◽  
De Lin ◽  
Alain-Pierre Petit ◽  
David W. Gray ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Mutational Analysis ◽  
Nonstructural Protein ◽  
Translation Efficiency ◽  
Screening Assay ◽  
High Throughput Screening Assay ◽  
Starting Point ◽  
Approved Drugs ◽  
High Throughput Assay

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) represents a significant threat to human health. Despite its similarity to related coronaviruses, there are currently no specific treatments for COVID-19 infection, and therefore there is an urgent need to develop therapies for this and future coronavirus outbreaks. Formation of the cap at the 5′ end of viral RNA has been shown to help coronaviruses evade host defenses. Nonstructural protein 14 (nsp14) is responsible for N7-methylation of the cap guanosine in coronaviruses. This enzyme is highly conserved among coronaviruses and is a bifunctional protein with both N7-methyltransferase and 3′-5′ exonuclease activities that distinguish nsp14 from its human equivalent. Mutational analysis of SARS-CoV nsp14 highlighted its role in viral replication and translation efficiency of the viral genome. In this paper, we describe the characterization and development of a high-throughput assay for nsp14 utilizing RapidFire technology. The assay has been used to screen a library of 1771 Food and Drug Administration (FDA)-approved drugs. From this, we have validated nitazoxanide as a selective inhibitor of the methyltransferase activity of nsp14. Although modestly active, this compound could serve as a starting point for further optimization.

scholarly journals REPURPOSING FDA-APPROVED DRUGS AGAINST MULTIPLE PROTEINS OF SARS-CoV-2: AN in silico STUDY

2021 ◽  
pp. e00845
Author(s):  
Alfred Olaoluwa Akinlalu ◽  
Annapoorna Chamundi ◽  
Donald Terseer Yakumbur ◽  
Funmilayo I. Deborah Afolayan ◽  
Ijeoma Akunna Duru ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Study ◽  
Approved Drugs ◽  
Fda Approved Drugs

In Silico Modeling of FDA-Approved Drugs for Discovery of Therapies Against Neglected Diseases: A Drug Repurposing Approach

2019 ◽  
pp. 625-648 ◽  
Author(s):  
Carolina L. Belllera ◽  
María L. Sbaraglini ◽  
Lucas N. Alberca ◽  
Juan I. Alice ◽  
Alan Talevi
Keyword(s):  
In Silico ◽  
Drug Repurposing ◽  
Neglected Diseases ◽  
In Silico Modeling ◽  
Approved Drugs ◽  
Fda Approved Drugs
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