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Morphogenetic (Mucin Expression) as Well as Potential Anti-Corona Viral Activity of the Marine Secondary Metabolite Polyphosphate on A549 Cells.
Müller, Werner E G; Neufurth, Meik; Wang, Shunfeng; Tan, Rongwei; Schröder, Heinz C; Wang, Xiaohong.
  • Müller WEG; ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, Germany.
  • Neufurth M; ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, Germany.
  • Wang S; ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, Germany.
  • Tan R; Shenzhen Lando Biomaterials Co., Ltd., Building B3, Unit 2B-C, China Merchants Guangming Science Park, Guangming District, Shenzhen 518107, China.
  • Schröder HC; ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, Germany.
  • Wang X; ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, Germany.
Mar Drugs ; 18(12)2020 Dec 14.
Article in English | MEDLINE | ID: covidwho-977761
ABSTRACT
The mucus layer of the nasopharynx and bronchial epithelium has a barrier function against inhaled pathogens such as the coronavirus SARS-CoV-2. We recently found that inorganic polyphosphate (polyP), a physiological, metabolic energy (ATP)-providing polymer released from blood platelets, blocks the binding of the receptor binding domain (RBD) to the cellular ACE2 receptor in vitro. PolyP is a marine natural product and is abundantly present in marine bacteria. Now, we have approached the in vivo situation by studying the effect of polyP on the human alveolar basal epithelial A549 cells in a mucus-like mucin environment. These cells express mucins as well as the ectoenzymes alkaline phosphatase (ALP) and adenylate kinase (ADK), which are involved in the extracellular production of ATP from polyP. Mucin, integrated into a collagen-based hydrogel, stimulated cell growth and attachment. The addition of polyP to the hydrogel significantly increased cell attachment and also the expression of the membrane-tethered mucin MUC1 and the secreted mucin MUC5AC. The increased synthesis of MUC1 was also confirmed by immunostaining. This morphogenetic effect of polyP was associated with a rise in extracellular ATP level. We conclude that the nontoxic and non-immunogenic polymer polyP could possibly also exert a protective effect against SARS-CoV-2-cell attachment; first, by stimulating the innate antiviral response by strengthening the mucin barrier with its antimicrobial proteins, and second, by inhibiting virus attachment to the cells, as deduced from the reduction in the strength of binding between the viral RBD and the cellular ACE2 receptor.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Polyphosphates / Biological Products / Respiratory Mucosa / Aquatic Organisms / COVID-19 Limits: Humans Language: English Journal subject: Biology / Pharmacology Year: 2020 Document Type: Article Affiliation country: Md18120639

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Polyphosphates / Biological Products / Respiratory Mucosa / Aquatic Organisms / COVID-19 Limits: Humans Language: English Journal subject: Biology / Pharmacology Year: 2020 Document Type: Article Affiliation country: Md18120639