Dengue virus (DENV) presents a significant threat to global public health with more than 500,000 hospitalizations and 25,000 deaths annually. Currently, there is no clinically approved antiviral drug to treat DENV infection. The envelope (E) glycoprotein of DENV is a promising target for drug discovery as the E protein is important for viral attachment and fusion. Understanding the structure and function of DENV E protein has led to the exploration of structure-based drug discovery of antiviral compounds and peptides against DENV infections. This review summarizes the structural information of the DENV E protein with regards to DENV attachment and fusion. The information enables the development of antiviral agents through structure-based approaches. In addition, this review compares the potency of antivirals targeting the E protein with the antivirals targeting DENV multifunctional enzymes, repurposed drugs and clinically approved antiviral drugs. None of the current DENV antiviral candidates possess potency similar to the approved antiviral drugs which indicates that more efforts and resources must be invested before an effective DENV drug materializes.

中文翻译：

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基于结构的抗登革病毒包膜糖蛋白抗病毒药物的设计。

登革热病毒（DENV）对全球公共健康构成了重大威胁，每年有500,000多例住院治疗和25,000例死亡。当前，尚无临床批准的抗病毒药物来治疗DENV感染。DENV的包膜（E）糖蛋白是药物发现的有希望的目标，因为E蛋白对于病毒的附着和融合很重要。了解DENV E蛋白的结构和功能已导致探索基于结构的药物发现抗DENV感染的抗病毒化合物和肽。这篇综述总结了有关DENV附着和融合的DENV E蛋白的结构信息。该信息可通过基于结构的方法来开发抗病毒药物。此外，这篇综述比较了针对E蛋白的抗病毒药与针对DENV多功能酶，改用药物和临床批准的抗病毒药的抗病毒药的功效。当前没有任何DENV抗病毒药物具有与批准的抗病毒药物相似的功效，这表明在有效的DENV药物出现之前必须投入更多的精力和资源。