Morphogenetic (Mucin Expression) as Well as Potential Anti-Corona Viral Activity of the Marine Secondary Metabolite Polyphosphate on A549 Cells.

Werner E G Müller,Meik Neufurth,Rongwei Tan,Heinz C Schröder,Xiaohong Wang,Shunfeng Wang

doi:10.3390/md18120639

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.

Highlights

Human viruses are obligate cell parasites that infect their target cells/tissues via specific portals of entry
The hydrogel-forming potential of collagen was exploited to provide a suitable scaffold for the A549
The role of the mucins is not restricted to the mechanical barrier function but at least the membrane-bound mucins such as MUC1 have signaling functions [62]

Summary

Introduction

Human viruses are obligate cell parasites that infect their target cells/tissues via specific portals of entry. They predominantly interact with the host epithelium, which lines both the outer surface and the inner cavities of the body. Among them is the mucosal epithelium, which is covered by a protective layer, the mucus This epithelium spans the respiratory tract, the gastrointestinal tract, and the genital tract. This cell barrier can be bypassed if the viruses can directly access the internal sites within the tissue, e.g., after biting of an insect or an animal, or through transplantation of a virally infected organ. Cell damage or cell death after a virus infection results in a shutdown of cellular

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