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  1. Article ; Online: N-Acetylcysteine and Other Sulfur-Donors as a Preventative and Adjunct Therapy for COVID-19.

    du Preez, Heidi N / Aldous, Colleen / Kruger, Hendrik G / Johnson, Lin

    Advances in pharmacological and pharmaceutical sciences

    2022  Volume 2022, Page(s) 4555490

    Abstract: ... where the degree and position of the sulfate groups determine the biological activity. N-acetylcysteine (NAC) and ...

    Abstract The airway epithelial glycocalyx plays an important role in preventing severe acute respiratory syndrome coronavirus 2 entry into the epithelial cells, while the endothelial glycocalyx contributes to vascular permeability and tone, as well as modulating immune, inflammatory, and coagulation responses. With ample evidence in the scientific literature that coronavirus disease 2019 (COVID-19) is related to epithelial and endothelial dysfunction, preserving the glycocalyx should be the main focus of any COVID-19 treatment protocol. The most studied functional unit of the glycocalyx is the glycosaminoglycan heparan sulfate, where the degree and position of the sulfate groups determine the biological activity. N-acetylcysteine (NAC) and other sulfur donors contribute to the inorganic sulfate pool, the rate-limiting molecule in sulfation. NAC is not only a precursor to glutathione but also converts to hydrogen sulfide, inorganic sulfate, taurine, Coenzyme A, and albumin. By optimising inorganic sulfate availability, and therefore sulfation, it is proposed that COVID-19 can be prevented or at least most of the symptoms attenuated. A comprehensive COVID-19 treatment protocol is needed to preserve the glycocalyx in both the prevention and treatment of COVID-19. The use of NAC at a dosage of 600 mg bid for the prevention of COVID-19 is proposed, but a higher dosage of NAC (1200 mg bid) should be administered upon the first onset of symptoms. In the severe to critically ill, it is advised that IV NAC should be administered immediately upon hospital admission, and in the late stage of the disease, IV sodium thiosulfate should be considered. Doxycycline as a protease inhibitor will prevent shedding and further degradation of the glycocalyx.
    Language English
    Publishing date 2022-08-10
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 3026687-7
    ISSN 2633-4690 ; 2633-4682 ; 2633-4690
    ISSN (online) 2633-4690 ; 2633-4682
    ISSN 2633-4690
    DOI 10.1155/2022/4555490
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Pathogenesis of COVID-19 described through the lens of an undersulfated and degraded epithelial and endothelial glycocalyx.

    du Preez, Heidi N / Aldous, Colleen / Hayden, Melvin R / Kruger, Hendrik G / Lin, Johnson

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology

    2021  Volume 36, Issue 1, Page(s) e22052

    Abstract: The glycocalyx surrounds every eukaryotic cell and is a complex mesh of proteins and carbohydrates. It consists of proteoglycans with glycosaminoglycan side chains, which are highly sulfated under normal physiological conditions. The degree of sulfation ... ...

    Abstract The glycocalyx surrounds every eukaryotic cell and is a complex mesh of proteins and carbohydrates. It consists of proteoglycans with glycosaminoglycan side chains, which are highly sulfated under normal physiological conditions. The degree of sulfation and the position of the sulfate groups mainly determine biological function. The intact highly sulfated glycocalyx of the epithelium may repel severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) through electrostatic forces. However, if the glycocalyx is undersulfated and 3-O-sulfotransferase 3B (3OST-3B) is overexpressed, as is the case during chronic inflammatory conditions, SARS-CoV-2 entry may be facilitated by the glycocalyx. The degree of sulfation and position of the sulfate groups will also affect functions such as immune modulation, the inflammatory response, vascular permeability and tone, coagulation, mediation of sheer stress, and protection against oxidative stress. The rate-limiting factor to sulfation is the availability of inorganic sulfate. Various genetic and epigenetic factors will affect sulfur metabolism and inorganic sulfate availability, such as various dietary factors, and exposure to drugs, environmental toxins, and biotoxins, which will deplete inorganic sulfate. The role that undersulfation plays in the various comorbid conditions that predispose to coronavirus disease 2019 (COVID-19), is also considered. The undersulfated glycocalyx may not only increase susceptibility to SARS-CoV-2 infection, but would also result in a hyperinflammatory response, vascular permeability, and shedding of the glycocalyx components, giving rise to a procoagulant and antifibrinolytic state and eventual multiple organ failure. These symptoms relate to a diagnosis of systemic septic shock seen in almost all COVID-19 deaths. The focus of prevention and treatment protocols proposed is the preservation of epithelial and endothelial glycocalyx integrity.
    MeSH term(s) COVID-19/metabolism ; COVID-19/pathology ; Endothelial Cells/metabolism ; Endothelial Cells/pathology ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/pathology ; Glycocalyx/metabolism ; Glycocalyx/pathology ; Glycocalyx/virology ; Humans ; Oxidative Stress ; SARS-CoV-2/metabolism ; Sulfotransferases/metabolism
    Chemical Substances Sulfotransferases (EC 2.8.2.-)
    Language English
    Publishing date 2021-12-01
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.202101100RR
    Database MEDical Literature Analysis and Retrieval System OnLINE

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