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      Advances in high‐resolution mass spectrometry applied to pharmaceuticals in 2020: A whole new age of information

      Author(s): 1 , 1
      Publication date (Electronic):
      Journal: Analytical Science Advances
      Publisher: Wiley

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          Abstract

          <p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d2012107e184">Continuous improvements in mass spectrometry (MS) have resulted in the widespread availability and adoption of high‐resolution mass spectrometry (HRMS) across laboratories worldwide. The capabilities and the associated advantages of HRMS make it an invaluable analytical tool for analyte characterization, screening, and quantification methodologies for a wide scope of applications across pharmaceutical development. These applications include drug discovery, product characterizations of both small molecules and novel drug modalities, <i>in vitro</i> and <i>in vivo</i> metabolism studies, post‐approval quality control, and pharmacovigilance. This review gives an overview of the current capabilities of HRMS and its pharmaceutical applications in 2020, and provides a perspective on the future of HRMS within the pharmaceutical industry. </p>

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          A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug-Repurposing

          David E Gordon, Gwendolyn M Jang, Mehdi Bouhaddou … (2020)
          SUMMARY The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption 1,2 . There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.
          Article 0 comments Cited 2298 times – based on 0 reviews     Review now
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            The Lancet Commission on pollution and health

            Philip J. Landrigan, Richard C. Fuller, Nereus J R Acosta … (2018)
            Article 0 comments Cited 974 times – based on 0 reviews     Review now
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              Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome

              C Wong, C W K Lam, A K L Wu … (2004)
              Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease caused by a novel coronavirus, but its immunopathological mechanisms have not yet been fully elucidated. We investigated changes in plasma T helper (Th) cell cytokines, inflammatory cytokines and chemokines in 20 patients diagnosed with SARS. Cytokine profile of SARS patients showed marked elevation of Th1 cytokine interferon (IFN)-γ, inflammatory cytokines interleukin (IL)-1, IL-6 and IL-12 for at least 2 weeks after disease onset, but there was no significant elevation of inflammatory cytokine tumour necrosis factor (TNF)-α, anti-inflammatory cytokine IL-10, Th1 cytokine IL-2 and Th2 cytokine IL-4. The chemokine profile demonstrated significant elevation of neutrophil chemokine IL-8, monocyte chemoattractant protein-1 (MCP-1), and Th1 chemokine IFN-γ-inducible protein-10 (IP-10). Corticosteroid reduced significantly IL-8, MCP-1 and IP-10 concentrations from 5 to 8 days after treatment (all P < 0·001). Together, the elevation of Th1 cytokine IFN-γ, inflammatory cytokines IL-1, IL-6 and IL-12 and chemokines IL-8, MCP-1 and IP-10 confirmed the activation of Th1 cell-mediated immunity and hyperinnate inflammatory response in SARS through the accumulation of monocytes/macrophages and neutrophils.
              Article 0 comments Cited 715 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Stephen W. Holman: (View ORCID Profile)
                Journal
                Title: Analytical Science Advances
                Abbreviated Title: Analytical Science Advances
                Publisher: Wiley
                ISSN (Print): 2628-5452
                ISSN (Electronic): 2628-5452
                Publication date Created: April 2021
                Publication date (Electronic): January 29 2021
                Publication date (Print): April 2021
                Volume: 2
                Issue: 3-4
                Pages: 142-156
                Affiliations
                [1 ]Chemical Development Pharmaceutical Technology &amp; Development Operations, AstraZeneca Macclesfield UK
                Article
                DOI: 10.1002/ansa.202000149
                SO-VID: 9b56877c-6069-41f3-a456-a07e093c0196
                Copyright © © 2021
                License:

                http://creativecommons.org/licenses/by/4.0/

                http://doi.wiley.com/10.1002/tdm_license_1.1

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