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Computational Screening of Approved Drugs for Inhibition of the Antibiotic Resistance Gene mecA in Methicillin-Resistant Staphylococcus aureus (MRSA) Strains.

Antibiotic resistance is a critical problem that results in a high morbidity and mortality rate. The process of discovering new chemotherapy and antibiotics is challenging, expensive, and time-consuming, with only a few getting approved for clinical use. Therefore, screening already-approved drugs to combat pathogens such as bacteria that cause serious infections in humans and animals is highly encouraged. In this work, we aim to identify approved antibiotics that can inhibit the mecA antibiotic resistance gene found in methicillin-resistant Staphylococcus aureus (MRSA) strains. The MecA prote

The nsp15 Nuclease as a Good Target to Combat SARS-CoV-2: Mechanism of Action and Its Inactivation with FDA-Approved Drugs.

The pandemic caused by SARS-CoV-2 is not over yet, despite all the efforts from the scientific community. Vaccination is a crucial weapon to fight this virus; however, we still urge the development of antivirals to reduce the severity and progression of the COVID-19 disease. For that, a deep understanding of the mechanisms involved in viral replication is necessary. nsp15 is an endoribonuclease critical for the degradation of viral polyuridine sequences that activate host immune sensors. This enzyme is known as one of the major interferon antagonists from SARS-CoV-2. In this work, a biochemica

Using in silico modelling and FRET-based assays in the discovery of novel FDA-approved drugs as inhibitors of MERS-CoV helicase.

A Förster resonance energy transfer (FRET)-based assay was used to screen the FDA-approved compound library against the MERS-CoV helicase, an essential enzyme for virus replication within the host cell. Five compounds inhibited the helicase activity with submicromolar potencies (IC50, 0.73-1.65 µM) and ten compounds inhibited the enzyme with micromolar potencies (IC50, 19.6-502 µM). The molecular operating environment (MOE) was used to dock the identified inhibitors on the MERS-CoV helicase nucleotide binding. Strong inhibitors docked well in the nucleotide-binding site and established interac

Deep-learning based repurposing of FDA-approved drugs against Candida albicans dihydrofolate reductase and molecular dynamics study.

Candida albicans causes the fatal fungal bloodstream infection in humans called Candidiasis. Most of the Candida species are resistant to the antifungals used to treat them. Drug-resistant C. albicans poses very serious public health issues. To overcome this, the development of effective drugs with novel mechanism(s) of action is requisite. Drug repurposing is considered a viable alternative approach to overcome the above issue. In the present study, we have attempted to identify drugs that could target the essential enzyme, dihydrofolate reductase of C. albicans (CaDHFR) to find out potent an

Suramin, screened from an approved drug library, inhibits HuR functions and attenuates malignant phenotype of oral cancer cells.

AU-rich elements (ARE) exist in the 3'-untranslated regions of the mRNA transcribed from cell growth-related genes such as proto-oncogenes, cyclin-related genes, and growth factors. HuR binds and stabilizes ARE-mRNA. HuR is expressed abundantly in cancer cells and related malignant phenotypes. HuR knockdown attenuates the malignant phenotype of oral cancer cells. In this study, we screened 1570 compounds in the approved drug library by differential scanning fluorimetry (DSF) to discover a HuR-targeted compound. Firstly, 55 compounds were selected by DSF. Then, 8 compounds that showed a shift i

Systematic Review of Efficacy and Safety of Newer Antidiabetic Drugs Approved from 2013 to 2017 in Controlling HbA1c in Diabetes Patients.

Type 2 Diabetes Mellitus (T2DM) is the most common form of diabetes mellitus and accounts for about 95% of all diabetes cases. Many newer oral as well as parenteral antidiabetic drugs have been introduced in to the market in recent years to control hyperglycemic conditions in diabetes patients and many of these drugs produce potential side effects in diabetes patients. Hence, this systematic review was aimed to analyze and compare the efficacy and safety of oral antidiabetic agents in controlling HbA1c in T2DM patients, that were approved by the United States-Food and Drug Administration (US-F

Prolonged use of the etonogestrel implant and levonorgestrel intrauterine device: 2 years beyond Food and Drug Administration-approved duration.

BACKGROUND: The subdermal contraceptive implant and the 52-mg levonorgestrel intrauterine device are currently Food and Drug Administration approved for 3 and 5 years of use, respectively. Limited available data suggested both of these methods are effective beyond that time. Demonstration of prolonged effectiveness will improve the cost-effectiveness of the device, and potentially patient continuation and satisfaction. OBJECTIVE: We sought to evaluate the effectiveness of the contraceptive implant and the 52-mg hormonal intrauterine device in women using the method for 2 years beyond the curr

Clinical performance of the Food and Drug Administration-Approved high-risk HPV test for the detection of high-grade cervicovaginal lesions.

BACKGROUND: In recent years, high-risk human papillomavirus (hrHPV) testing for triaging atypical squamous cells of undetermined significance and cotesting with cytology have been implemented in clinical practice. However, clinical data for primary screening with human papillomavirus (HPV) testing alone are currently lacking. METHODS: This study retrospectively reviewed the correlation of cytology, histology, and hrHPV testing through the use of a cytology laboratory quality assurance database with 130,648 Papanicolaou (Pap) tests interpreted at Houston BioReference Laboratories and Houston M

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

The constitutively active fusion protein BCR-ABL1 is the major cause of chronic myeloid leukemia (CML), and selective inhibition of ABL1 is a promising approach for the treatment of CML. Reported drugs worked well in clinical practice, such as imatinib, dasatinib, nilotinib and bosutinib. However, resistance arises due to ABL1 mutation in patients, especially the T315I gate-keeper mutation. Thus, wide spectrum drugs targeting ABL1 are urgently needed. In order to screen potential drugs targeting wild-type ABL1 and T315I mutant ABL1, 1408 FDA approved small molecule drugs were subjected to mole

US Food and Drug Administration /Conformit Europe- approved absorbable nerve conduits for clinical repair of peripheral and cranial nerves.

Several absorbable nerve conduits are approved by the US Food and Drug Administration (FDA) and Conformit Europe (CE) for clinical repair of peripheral and cranial nerves . Surgeons are often not aware of the different(bio) materials of these conduits when performing nerve repair. An overview of these FDA- and CE-approved absorbable nerve conduits for clinical use is presented . PubMed, MEDLINE, and the companies selling the conduits were consulted . The available FDA and CE absorbable nerve conduits for peripheral and cranial nerve repair are 2 collagen- and 2 synthetic- polyester based condu

Identification of FDA approved drugs against SARS-CoV-2 RNA dependent RNA polymerase (RdRp) and 3-chymotrypsin-like protease (3CLpro), drug repurposing approach.

The RNA-dependent RNA polymerase (RdRp) and 3C-like protease (3CLpro) from SARS-CoV-2 play crucial roles in the viral life cycle and are considered the most promising targets for drug discovery against SARS-CoV-2. In this study, FDA-approved drugs were screened to identify the probable anti-RdRp and 3CLpro inhibitors by molecular docking approach. The number of ligands selected from the PubChem database of NCBI for screening was 1760. Ligands were energy minimized using Open Babel. The RdRp and 3CLpro protein sequences were retrieved from the NCBI database. For Homology Modeling predictions, w

Drug repurposing strategy to identify the putative leads against the Epidermal growth factor receptor (EGFR) from the USFDA-approved drug pool: Investigating the utility as an anticancer agent.

EGFR is a validated drug target in anticancer drug discovery. However, the existing issues of drug resistance, toxicities, and evolving mutations in EGFR have led to the global decline in the putative and potent anti-EGFR therapeutics. To address this gap, drug repurposing or repositioning is a valid technique for drug identification in a quick time and in an economical way. We herein employed the drug repurposing techniques from the library of 3500 approved USFDA small molecules. The initial HTVS (high-throughput virtual screening), followed by XP analysis and molecular mechanics (MMGBSA) and

Small-Incision Lenticule Extraction (SMILE) for the Correction of Myopia with Astigmatism: Outcomes of the United States Food and Drug Administration Premarket Approval Clinical Trial.

PURPOSE: To present outcomes of the United States Food and Drug Administration premarket approval clinical trial of small-incision lenticule extraction (SMILE) for the correction of myopia and astigmatism. DESIGN: Prospective, multicenter clinical trial. PARTICIPANTS: The study included 357 eyes of 357 patients treated with SMILE (50 for myopia and 307 for myopia with astigmatism). Preoperative sphere ranged between -1.00 and -10.00 diopters (D), with manifest spherical equivalent (MSE) of up to -11.50 D and refractive cylinder of up to -3.00 D. METHODS: -Participants were followed up for 1

Assessment of Use of Combined Dextromethorphan and Quinidine in Patients With Dementia or Parkinson Disease After US Food and Drug Administration Approval for Pseudobulbar Affect.

IMPORTANCE: In 2010, the US Food and Drug Administration (FDA) approved a combination of dextromethorphan hydrobromide and quinidine sulfate for the treatment of pseudobulbar affect after studies in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). This medication, however, may be commonly prescribed in patients with dementia and/or Parkinson disease (PD). OBJECTIVE: To investigate the prescribing patterns of dextromethorphan-quinidine, including trends in associated costs. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study of patients prescribe

Repurposing approved drugs as Pendrin (SLC26A4) inhibitors in allergic asthma: single-cell nomination, structure-based screening and functional validation.

Type-2 airway inflammation remodels the airway epithelium and drives mucus-associated transcriptional programs, making the epithelium an attractive source of drug targets in allergic asthma. Reanalyzing GSE193816, a lower-airway single-cell RNA-seq dataset of allergic asthma (AA) and allergic non-asthma control (AC) participants sampled before and after allergen challenge, a systematic epithelial prioritization ranked SLC26A4/Pendrin highly among asthma-enriched candidates, consistent with its previously reported induction in asthmatic airway epithelium. SLC26A4 was epithelial-biased, was stro

Efficacy and Safety Evidence Supporting Cancer Drug Approvals in Switzerland (2001-2020): A Meta-Analysis of Pivotal Randomised Controlled Trials.

BACKGROUND: Randomised controlled trials (RCTs) with overall survival (OS) as the primary endpoint remain the gold standard for evaluating the efficacy and safety of new cancer therapies. However, increasing reliance on early or intermediate endpoints such as progression- or recurrence-related time-to-event endpoints (PRTTE) including progression-free survival (PFS) and disease-free survival (DFS) has led to concerns about the strength and clinical relevance of the evidence at the time of approval. We aimed to systematically evaluate the evidence supporting new cancer drugs approved by Swissme

Совпадение в полном тексте источника
… Despite systematic evaluations of the evidence supporting cancer drug approvals by the U.S. … Table 1 Characteristics of pivotal randomised controlled trials supporting cancer drug approvals in Switzerland, 2001–2020. …

Repositioning FDA-Approved Sulfonamide-Based Drugs as Potential Carbonic Anhydrase Inhibitors in Trypanosoma cruzi: Virtual Screening and In Vitro Studies.

Background/Objectives: α-carbonic anhydrase (α-TcCA) has emerged as a promising drug target in T. cruzi, the causative agent of Chagas disease in the Americas. Sulfonamides, known inhibitors of CAs, bind to the zinc ion on the enzyme's active site. This study proposes the repositioning of sulfonamide-based drugs to identify new trypanocidal agents. Method: Ligand-based virtual screening and molecular docking analysis were performed on FDA-approved drugs targeting α-TcCA. These compounds were evaluated in vitro and ex vivo against the A1 and NINOA strains, followed by enzymatic assays. Results: