: Acquired Immune Deficiency Syndrome (AIDS) is a devastating infectious disease caused by the Human Immunodeficiency Virus type 1 (HIV-1). Enfuvirtide(T20) is the first HIV-1 fusion inhibitor for marketing, which plays an important role in AIDS treatment. However, in the clinical application process, T20 has several drawbacks, such as a high level of development of drug resistance, a short half-life in vivo, and rapid renal clearance, which severely limits the clinical application. Therefore, the development of novel fusion inhibitors to address T20 shortcomings has long been the research hotspot. Short peptides have a long half-life through modification and a high barrier to drug resistance, which is expected to solve the current fusion inhibitors dilemma. In this paper, we summarized six emerging R&D strategies for short peptide-based fusion inhibitors against HIV-1. We hope that this review will provide fresh insights into the development of novel fusion inhibitors, as well as ideas for other viral fusion inhibitor discoveries based on the common membrane fusion 6-HB core structure.

中文翻译：

---

基于6-HB核心结构的抗HIV-1短肽融合抑制剂的研究策略：综述

：获得性免疫缺陷综合症 (AIDS) 是一种由 1 型人类免疫缺陷病毒 (HIV-1) 引起的毁灭性传染病。恩夫韦肽（T20）是第一个上市的HIV-1融合抑制剂，在艾滋病治疗中发挥着重要作用。但在临床应用过程中，T20存在耐药性高、体内半衰期短、肾脏清除快等缺点，严重限制了其临床应用。因此，开发新型融合抑制剂来解决T20的缺点一直是研究热点。短肽通过修饰具有较长的半衰期和较高的耐药屏障，有望解决目前融合抑制剂的困境。在本文中，我们总结了针对 HIV-1 的短肽融合抑制剂的六种新兴研发策略。我们希望这篇综述能够为新型融合抑制剂的开发提供新的见解，并为基于常见膜融合6-HB核心结构的其他病毒融合抑制剂的发现提供思路。