The SARS-CoV-2 Entry Inhibition Mechanisms of Serine Protease Inhibitors, OM-85, Heparin and Soluble HS Might Be Linked to HS Attachment Sites

Abstract

This article discusses the importance of D-xylose for fighting viruses (especially SARS-CoV-2) that use core proteins as receptors at the cell surface, by providing additional supporting facts that these viruses probably bind at HS/CS attachment sites (i.e., the hydroxyl groups of Ser/Thr residues of the core proteins intended to receive the D-xylose molecules to initiate the HS/CS chains). Essentially, the additional supporting facts, are: some anterior studies on the binding sites of exogenous heparin and soluble HS on the core proteins, the inhibition of the viral entry by pre-incubation of cells with heparin, and additionally, corroborating studies about the mechanism leading to type 2 diabetes during viral infection. We then discuss the mechanism by which serine protease inhibitors inhibit SARS-CoV-2 entry. The biosynthesis of heparan sulfate (HS), chondroitin sulfate (CS), dermatan sulfate (DS), and heparin (Hep) is initiated not only by D-xylose derived from uridine diphosphate (UDP)-xylose, but also bioactive D-xylose molecules, even in situations where cells were previously treated with GAG inhibitors. This property of D-xylose shown by previous anterior studies helped in the explanation of the mechanism leading to type 2 diabetes during SARS-CoV-2 infection. This explanation is completed here by a preliminary estimation of xyloside GAGs (HS/CS/DS/Hep) in the body, and with other previous studies helping to corroborate the mechanism by which the D-xylose exhibits its antiglycaemic properties and the mechanism leading to type 2 diabetes during SARS-CoV-2 infection. This paper also discusses the confirmatory studies of regarding the correlation between D-xylose and COVID-19 severity.

Gold-Based Metal Drugs as Inhibitors of Coronavirus Proteins: The Inhibition of SARS-CoV-2 Main Protease by Auranofin and Its Analogs

“…To this end, expanding the chemical space of the tested compounds by including a large variety of metal compounds is highly desirable. It has to be stressed that the search for efficient inhibitors of SARS-CoV-2-related proteases has almost entirely focused on organic molecules [ 2 , 3 , 4 ]; much less attention has been deserved so far to inorganic moieties [ 5 , 6 ] that merit, in our opinion, a greater consideration.…”

Polysaccharides and Lectins: A Natural Complementary Approach against the SARS-CoV-2 Pandemic

“…The linear highly sulfated glycosaminoglycans units of heparin are known as heparan sulfates (HSs) [49]. Besides a variety of beneficial physiological roles derived from its binding ability at the surface of cells [50], heparins, however, particularly the heparan sulfate, act as first pathogen receptors enabling the coronavirus to anchor to its proteoglycans before interacting with the ACE2 entry receptor of the host cells (Table 1) [51][52][53][54]. Multiple binding motif sequences have been identified at different sites within the SARS-CoV-2 spike S-protein receptor-binding domain, such as the S1/S2 proteolytic cleavage motif and Y453-S459 and P681-S686, S2 ′ proteolytic cleavage S810-S816, [55,56] or near various amino acid-rich residues in different Omicron variants [57].…”

“…However, the versatility of heparin as an effective inhibitor of viral attachment was also suggested based on its polyanionic nature from as early as 2020 [58]. The use of soluble HS and other xyloside GAGs, such as heparin, dermatan, and chondroitin sulfates as competitive inhibitors to SARS-CoV-2, preventing the binding at the HS attachment sites, is suggested [53] based on recent evidence [59]. Preclinical evidence was brought by a series of studies that reported that exogenous heparin and derivatives such as enoxaparin can inhibit the viral infection by inducing conformational changes in the spike protein receptor-binding domain S1 in a dosedependent manner and at concentrations used during anti-coagulation therapy [59,60].…”

Studies on the Changes of Fermentation Metabolites and the Protective Effect of Fermented Edible Grass on Stress Injury Induced by Acetaminophen in HepG2 Cells

“…Trehalose can be obtained from the conversion of glucose by trehalose synthase with the action of microorganisms [20], which was effective on atherosclerosis and postinfarct cardiomyopathy [21,22]. D-xylose played a major role in hypoglycemic activity and antiviral activity [23], and the increase in its level was probably attributed to the release action from hemicellulose by fermentation on edible grass.…”