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Review
. 2022 Aug 10:2022:4555490.
doi: 10.1155/2022/4555490. eCollection 2022.

N-Acetylcysteine and Other Sulfur-Donors as a Preventative and Adjunct Therapy for COVID-19

Heidi N du Preez  1 , Colleen Aldous  2 , Hendrik G Kruger  1 , Lin Johnson  3
Affiliations
Review

N-Acetylcysteine and Other Sulfur-Donors as a Preventative and Adjunct Therapy for COVID-19

Heidi N du Preez et al. Adv Pharmacol Pharm Sci. .

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.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic presentation of the epithelial glycocalyx (GL) in mammalian cells, forming a mesh-like structure that projects into the extracellular matrix (ECM). The proteoglycan presented is a syndecan with heparan sulfate and chondroitin sulfate glycosaminoglycan (GAG) side chains. The sulfate groups (SO42−) are indicated in red dots, attached to the GAG and glycoprotein side chains. Hyaluronic acid is unsulfated and anchored to the receptor CD44 on the cell membrane. The glycoprotein consists of a protein base with carbohydrate chains (orange circles) extending into the extracellular space with sialic acid (orange square) bound at the terminal position of the oligosaccharide chains. Soluble proteoglycans and free GAG chains can appear in the extracellular space.
Figure 2
Figure 2
Sulfur metabolism diagram. The essential sulfur amino acid methionine converts to cysteine, a precursor to albumin, cystine, coenzyme A, glutathione, hydrogen sulfite (H2S), taurine, and sulfate (SO42−). H2S can convert to thiosulfate (S2O32−) and sulfite (SO32−), which are oxidised to sulfate. The enzyme cystathionine-β-synthase (CBS) converts homocysteine to cystathionine, while cysteine dioxygenase (CDO) is responsible for the conversion of cysteine to cysteine sulfinic acid. Sulfite oxidase (SUOX) oxidises sulfite to sulfate. H2S is generated from cysteine by three different pathways through either CBS, cystathionine-γ-lyase (CSE), or 3-mercaptopyruvate sulfurtransferase (3-MST). Adapted with permission by CC by 4.0 [3].
See this image and copyright information in PMC

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