D-Xylose, a Stimulator of Heparan Sulfate Biosynthesis, Exhibits Antiviral Properties Against SARS-CoV-2, ZIKV, HCMV and HIV-1 NL4-3 In Vitro

Abstract

Background Primary human cytomegalovirus (HCMV) infection can be especially serious in pregnant women and cause severe consequences for newborns. We aimed to determine which metabolites, among the thousands in human sera, are strongly correlated with serious outcomes for pregnant women with HCMV. During the early stage of the pandemic, it was predicted that COVID-19 severity is correlated with serum D-xylose/xylitol levels, which has now been confirmed in two studies. Methods Between July 2022 and February 2023, four antiviral assays were performed by Virology Research Services Ltd. to test the antiviral activities of D-xylose, a small bioactive molecule, alone or in combination with insulin against HCMV in HFF, HIV-1 NL4-3 in HeLa TZM-bl, and ZIKV African strain and SARS-CoV-2 England strain separately in VeroE6, with incubation durations of 5 days, 48 h, 48 h and 72 h post-infection, respectively. Ganciclovir, 3′-Azido-3′-deoxythymidine (AZT), monensin and remdesivir were used as controls. An immunofluorescence method was used for readouts of all viruses except for SARS-CoV-2, for which CPE was considered. Cytotoxicity was assessed by an MTT assay. Results The results show that D-xylose exhibits antiviral activities against SARS-CoV-2, ZIKV, HCMV and HIV-1 in vitro, with preliminary selectivity indices of 11.6, 1.6, 2.1 and 2.6, respectively. Thus, D-xylose is more effective over a broader range of concentrations against HCMV and SARS-CoV-2 than against ZIKV and HIV-1. The EC50 value (in mM) for different assays must be placed in perspective; the average serum concentration of D-xylose in a healthy person is approximately 1.8 Mm. Conclusions The properties of the cell-layer HS stimulated by D-xylose and especially unfractionated heparin (UFH)—another antiviral compound against these viruses—combined with these results challenge the conclusion that HS promotes viral infections. Trial Registration Not Applicable.