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Lung Surfactant Protein B Peptide Mimics Interact with the Human ACE2 Receptor.
Waring, Alan J; Jung, Grace C-L; Sharma, Shantanu K; Walther, Frans J.
Afiliación
  • Waring AJ; Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Jung GC; The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
  • Sharma SK; Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Walther FJ; Materials and Process Simulation Center, California Institute of Technology, Pasadena, CA 91125, USA.
Int J Mol Sci ; 24(13)2023 Jun 29.
Article en En | MEDLINE | ID: mdl-37446012
Lung surfactant is a complex mixture of phospholipids and surfactant proteins that is produced in alveolar type 2 cells. It prevents lung collapse by reducing surface tension and is involved in innate immunity. Exogenous animal-derived and, more recently, synthetic lung surfactant has shown clinical efficacy in surfactant-deficient premature infants and in critically ill patients with acute respiratory distress syndrome (ARDS), such as those with severe COVID-19 disease. COVID-19 pneumonia is initiated by the binding of the viral receptor-binding domain (RBD) of SARS-CoV-2 to the cellular receptor angiotensin-converting enzyme 2 (ACE2). Inflammation and tissue damage then lead to loss and dysfunction of surface activity that can be relieved by treatment with an exogenous lung surfactant. Surfactant protein B (SP-B) is pivotal for surfactant activity and has anti-inflammatory effects. Here, we study the binding of two synthetic SP-B peptide mimics, Super Mini-B (SMB) and B-YL, to a recombinant human ACE2 receptor protein construct using molecular docking and surface plasmon resonance (SPR) to evaluate their potential as antiviral drugs. The SPR measurements confirmed that both the SMB and B-YL peptides bind to the rhACE2 receptor with affinities like that of the viral RBD-ACE2 complex. These findings suggest that synthetic lung surfactant peptide mimics can act as competitive inhibitors of the binding of viral RBD to the ACE2 receptor.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Surfactantes Pulmonares / COVID-19 Límite: Animals / Humans Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Surfactantes Pulmonares / COVID-19 Límite: Animals / Humans Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza