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

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.

Antiviral strategies should focus on stimulating the biosynthesis of heparan sulfates, not their inhibition.

Antiviral strategies for viruses that utilize proteoglycan core proteins (syndecans and glypicans) as receptors should focus on heparan sulfate (HS) biosynthesis rather than on inhibition of these sugar chains. Here, we show that heparin and certain xylosides, which exhibit in vitro viral entry inhibitory properties against HSV-1, HSV-2, HPV-16, HPV-31, HVB, HVC, HIV-1, HTLV-1, SARS-CoV-2, HCMV, DENV-1, and DENV-2, stimulated HS biosynthesis at the cell surface 2- to 3-fold for heparin and up to 10-fold for such xylosides. This is consistent with the hypothesis from a previous study that for core protein attachment, viruses are glycosylated at HS attachment sites (i.e., serine residues intended to receive the D-xylose molecule for initiating HS chains). Heparanase overexpression, endocytic entry, and syndecan shedding enhancement, all of which are observed during viral infection, lead to glycocalyx deregulation and appear to be direct consequences of this hypothesis. In addition to the appearance of type 2 diabetes and the degradation of HS observed during viral infection, we linked this hypothesis to that proposed in a previous publication.

Correlation of D-xylose with severity and morbidity-related factors of COVID-19 and possible therapeutic use of D-xylose and antibiotics for COVID-19.

The SARS-Cov-2 pandemic that currently affects the entire world has been shown to be especially dangerous in the elderly (≥65 years) and in smokers, with notably strong comorbidity in patients already suffering from chronic diseases, such as Type 2 diabetes, cancers, chronic respiratory diseases, obesity, and hypertension. Inflammation of the lungs is the main factor leading to respiratory distress in patients with chronic respiratory disease and in patients with severe COVID-19. Several studies have shown that inflammation of the lungs in general and Type 2 diabetes are accompanied by the degradation of glycosaminoglycans (GAGs), especially heparan sulfate (HS). Several studies have also shown the importance of countering the degradation of HS in lung infections and Type 2 diabetes. D-xylose, which is the initiating element for different sulfate GAG chains (especially HS), has shown regeneration properties for GAGs. D-xylose and xylitol have demonstrated anti-inflammatory, antiglycemic, antiviral, and antibacterial properties in lung infections, alone or in combination with antibiotics. Considering the existing research on COVID-19 and related to D-xylose/xylitol, this review offers a perspective on why the association between D-xylose and antibiotics may contribute to significantly reducing the duration of treatment of COVID-19 patients and why some anti-inflammatory drugs may increase the severity of COVID-19. A strong correlation with scurvy, based on gender, age, ethnicity, smoking status, and obesity status, is also reviewed. Related to this, the effects of treatment with plants such as Artemisia are also addressed. CHEMICAL COMPOUNDS: D-xylose; xylitol; l-ascorbic Acid; D-glucuronic acid; N-acetylglucosamine; D-N-acetylglucosamine; N-acetylgalactosamine; galactose.