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Sökning: L773:2374 7943 > (2022)

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1.
  • Guimond, S. E., et al. (författare)
  • Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction
  • 2022
  • Ingår i: ACS Central Science. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 8:5, s. 527-545
  • Tidskriftsartikel (refereegranskat)abstract
    • Heparan sulfate (HS) is a cell surface polysaccharide recently identified as a coreceptor with the ACE2 protein for the S1 spike protein on SARS-CoV-2 virus, providing a tractable new therapeutic target. Clinically used heparins demonstrate an inhibitory activity but have an anticoagulant activity and are supply-limited, necessitating alternative solutions. Here, we show that synthetic HS mimetic pixatimod (PG545), a cancer drug candidate, binds and destabilizes the SARS-CoV-2 spike protein receptor binding domain and directly inhibits its binding to ACE2, consistent with molecular modeling identification of multiple molecular contacts and overlapping pixatimod and ACE2 binding sites. Assays with multiple clinical isolates of SARS-CoV-2 virus show that pixatimod potently inhibits the infection of monkey Vero E6 cells and physiologically relevant human bronchial epithelial cells at safe therapeutic concentrations. Pixatimod also retained broad potency against variants of concern (VOC) including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Furthermore, in a K18-hACE2 mouse model, pixatimod significantly reduced SARS-CoV-2 viral titers in the upper respiratory tract and virus-induced weight loss. This demonstration of potent anti-SARS-CoV-2 activity tolerant to emerging mutations establishes proof-of-concept for targeting the HS-Spike protein-ACE2 axis with synthetic HS mimetics and provides a strong rationale for clinical investigation of pixatimod as a potential multimodal therapeutic for COVID-19.
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2.
  • Huang, Xiaofeng, et al. (författare)
  • Solvent Gaming Chemistry to Control the Quality of Halide Perovskite Thin Films for Photovoltaics
  • 2022
  • Ingår i: ACS CENTRAL SCIENCE. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 8:7, s. 1008-1016
  • Tidskriftsartikel (refereegranskat)abstract
    • Research on solvent chemistry, particularly for halide perovskite intermediates, has been advancing the development of perovskite solar cells (PSCs) toward commercial applications. A predictive understanding of solvent effects on the perovskite formation is thus essential. This work systematically discloses the relationship among the basicity of solvents, solvent-contained intermediate structures, and intermediate-to-perovskite alpha-FAPbI(3) evolutions. Depending on their basicity, solvents exhibit their own favorite bonding selection with FA(+) or Pb2+ cations by forming either hydrogen bonds or coordination bonds, resulting in two different kinds of intermediate structures. While both intermediates can be evolved into alpha-FAPbI(3) below the delta-to-alpha thermodynamic temperature, the hydrogen-bond-favorable kind could form defect-less alpha-FAPbI(3) via sidestepping the break of strong coordination bonds. The disclosed solvent gaming mechanism guides the solvent selection for fabricating high-quality perovskite films and thus high-performance PSCs and modules.
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  • Resultat 1-4 av 4

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