La COLOMBE Health Center, Fokoue - Cameroon, 7 rue Eric Tabarly, 91 300 Massy, France.
Life Sci. 2021 Jul 15;277:119508. doi: 10.1016/j.lfs.2021.119508. Epub 2021 Apr 15.
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.
利用蛋白聚糖核心蛋白（连接蛋白和聚糖蛋白）作为受体的病毒的抗病毒策略应侧重于肝素硫酸盐（HS）的生物合成，而不是抑制这些糖链。在这里，我们表明肝素和某些木糖苷，其在体外对 HSV-1、HSV-2、HPV-16、HPV-31、HBV、HCV、HIV-1、HTLV-1、SARS-CoV-2、HCMV、DENV-1 和 DENV-2 具有抑制病毒进入的特性，可在细胞表面将 HS 生物合成刺激 2-3 倍，而对于这些木糖苷，则可刺激高达 10 倍。这与之前研究中的假设一致，即对于核心蛋白附着，病毒在 HS 附着位点发生糖基化（即，用于启动 HS 链的丝氨酸残基接收 D-木糖分子）。肝素酶过表达、内吞进入和连接蛋白脱落增强，这些都在病毒感染过程中观察到，导致糖萼失调，这似乎是该假设的直接后果。除了在病毒感染过程中观察到 2 型糖尿病和 HS 的降解外，我们还将这一假设与之前发表的一篇论文中的假设联系起来。
