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靶向溶质载体(SLC)超家族的抗病毒治疗:作用机制与药物研发展望

Targeting the Solute Carrier (SLC) Superfamily for Antiviral Therapy: Mechanisms of Action and Drug Discovery Perspectives

  • 摘要: 溶质载体转运蛋白(solute carrier, SLC)超家族具有超过450个转运蛋白,在营养吸收、转运调控和免疫代谢中发挥关键作用,与多种疾病密切相关。本文系统综述了SLCs在抗病毒研究领域的最新研究进展,重点从以下三个机制展开阐述:首先,SLCs作为病毒入侵的关键细胞膜受体或协同因子,介导病毒与宿主细胞膜的吸附与融合;其次,SLCs通过调控宿主天然免疫信号通路,正向或负向调节抗病毒免疫应答;最后,SLCs作为抗病毒药物的跨膜转运体,决定药物的吸收、分布及代谢过程,从而显著影响药效。此外,本文总结了基于上述机制的宿主靶向抗病毒策略及相关活性分子的化学结构。最后,深入探讨了靶向SLCs开发新型抗病毒药物的潜力与面临的成药性挑战,为相关药物的分子设计与研发提供理论依据。

     

    Abstract: The solute carrier (SLC) superfamily, comprising over 450 transporter proteins, plays pivotal roles in nutrient absorption, transmembrane transport regulation, and immunometabolism, and is intimately linked to various pathological processes. This review systematically summarizes the latest progress of SLCs in the antiviral field, focusing on three classification mechanisms: firstly, SLCs function as critical receptors or cofactors for viral entry, mediating virus-host membrane adsorption and fusion; secondly, SLCs modulate host innate immune signaling pathways, thereby positively or negatively regulating antiviral immune responses; and thirdly, SLCs serve as transmembrane transporters for antiviral agents, determining their absorption, distribution, and metabolism (ADME) processes, which significantly influence therapeutic efficacy. Furthermore, host-targeted antiviral strategies based on these mechanisms and the chemical structures of relevant molecules are systematically elucidated. Finally, the potential of targeting SLCs for novel antiviral drug development and the associated druggability challenges are discussed in depth, providing a theoretical basis for the molecular design and development of next-generation antiviral agents..

     

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