A brief alcohol intervention during smoking cessation treatment in daily cigarette smokers: A pilot randomized controlled trial.

Alcohol use attenuates successful smoking cessation. We examined the feasibility, acceptability, and preliminary efficacy of a brief alcohol intervention in smokers. In this two-arm, assessor-blinded randomized controlled trial, we randomized 100 daily smokers (82.

Discovery of Anti-SARS-CoV-2 Nsp9 Binders from Natural Products by a Native Mass Spectrometry Approach.

The search for effective antiviral agents against SARS-CoV-2 remains a critical global endeavor. In this study, we focused on the viral nucleocapsid protein Nsp9, which is a key player in viral RNA replication and an attractive drug target. Employing a two-pronged approach, an in-house natural product library was screened using native mass spectrometry to identify compounds capable of binding to Nsp9.

Collision-Induced Affinity Selection Mass Spectrometry for Identification of Ligands.

Hyphenated mass spectrometry has been used to identify ligands binding to proteins. It involves mixing protein and compounds, separation of protein-ligand complexes from unbound compounds, dissociation of the protein-ligand complex, separation to remove protein, and injection of the supernatant into a mass spectrometer to observe the ligand. Here we report collision-induced affinity selection mass spectrometry (CIAS-MS), which allows separation and dissociation inside the instrument.

Discovery of a Natural Product That Binds to the Protein Rv1466 Using Native Mass Spectrometry.

Elucidation of the mechanism of action of compounds with cellular bioactivity is important for progressing compounds into future drug development. In recent years, phenotype-based drug discovery has become the dominant approach to drug discovery over target-based drug discovery, which relies on the knowledge of a specific drug target of a disease. Still, when targeting an infectious disease via a high throughput phenotypic assay it is highly advantageous to identifying the compound's cellular activity.

A Phenotarget Approach for Identifying an Alkaloid Interacting with the Tuberculosis Protein Rv1466.

In recent years, there has been a revival of interest in phenotypic-based drug discovery (PDD) due to target-based drug discovery (TDD) falling below expectations. Both PDD and TDD have their unique advantages and should be used as complementary methods in drug discovery. The PhenoTarget approach combines the strengths of the PDD and TDD approaches.

Development of an HPLC-based guanosine monophosphate kinase assay and application to Plasmodium vivax guanylate kinase.

The development of a high-performance liquid chromatography (HPLC)-based method, for guanosine monophosphate kinase activity assays, is presented. The method uses the intrinsic UV absorption (at 260 nm) of substrates and products of the enzymatic reaction (GMP, ATP, ADP and GDP) to unambiguously determine percent conversion of substrate into product. It uses a commercially available C18 column which can separate reaction samples by elution under isocratic conditions in 12 min per run.

Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry.

Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets.