Department of Medical Biochemistry and Microbiology, The Biomedical Center, University of Uppsala, Uppsala, Sweden.
Zoonosis Science Center, University of Uppsala, Uppsala, Sweden.
Am J Physiol Cell Physiol. 2022 Apr 1;322(4):C605-C613. doi: 10.1152/ajpcell.00028.2022. Epub 2022 Feb 23.
Heparan sulfate (HS) is a linear polysaccharide attached to a core protein, forming heparan sulfate proteoglycans (HSPGs) that are ubiquitously expressed on the surface of almost all mammalian cells and the extracellular matrix. HS orchestrates the binding of various signal molecules to their receptors, thus regulating many biological processes, including homeostasis, metabolism, and various pathological processes. Due to its wide distribution and negatively charged properties, HS is exploited by many viruses as a cofactor to attach to host cells. Therefore, inhibition of the interaction between virus and HS is proposed as a promising approach to mitigate viral infection, including SARS-CoV-2. In this review, we summarize the interaction manners of HS with viruses with focus on significant pathogenic RNA viruses, including alphaviruses, flaviviruses, and coronaviruses. We also provide an overview of the challenges we may face when using HS mimetics as antivirals for clinical treatment. More studies are needed to provide a further understanding of the interplay between HS and viruses both in vitro and in vivo, which will favor the development of specific antiviral inhibitors.
硫酸乙酰肝素（HS）是一种连接到核心蛋白上的线性多糖，形成硫酸乙酰肝素蛋白聚糖（HSPGs），广泛表达于几乎所有哺乳动物细胞表面和细胞外基质中。HS 协调各种信号分子与其受体的结合，从而调节许多生物学过程，包括内稳态、代谢和各种病理过程。由于其广泛的分布和负电荷特性，HS 被许多病毒用作辅助因子来附着于宿主细胞。因此，抑制病毒与 HS 的相互作用被提出作为减轻病毒感染的一种有前途的方法，包括 SARS-CoV-2。在这篇综述中，我们总结了 HS 与病毒的相互作用方式，重点关注重要的致病性 RNA 病毒，包括甲病毒、黄病毒和冠状病毒。我们还概述了在将 HS 类似物用作抗病毒临床治疗时可能面临的挑战。需要更多的研究来提供对 HS 与病毒之间在体外和体内相互作用的进一步理解，这将有利于开发特定的抗病毒抑制剂。
