Peptide-based Fusion Inhibitors for Preventing the Six-helix Bundle Formation of Class I Fusion Proteins: HIV and Beyond.
Peptide-based Fusion Inhibitors for Preventing the Six-helix Bundle Formation of Class I Fusion Proteins: HIV and Beyond.
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DOI：
10.2174/1570162x19666210908115231
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发表时间：
2021
影响因子：
1
通讯作者：
Hicar MD
中科院分区：
文献类型：
--
作者：
Monteiro A;Yu KOA;Hicar MD
许多不同的病毒家族已经开发出融合的方法来感染细胞。I类融合蛋白通常由沙粒病毒科、冠状病毒科、丝状病毒科、正粘病毒科、副粘病毒科和逆转录病毒科的成员使用。I类病毒融合蛋白是参与识别细胞受体的三聚体，具有负责融合病毒和靶细胞膜的区域。在融合过程中，融合区域折叠成六螺旋束（6HB），其接近导致融合的两个膜。对于人类免疫缺陷病毒（HIV），gp41亚基负责形成这种6HB。融合抑制剂药物恩夫韦肽或T20是美国食品和药物管理局和欧洲药品管理局批准的唯一一种针对这一关键步骤的药物，自2003年3月以来已广泛用于治疗艾滋病毒的联合方案。在这篇综述中，我们描述了基于肽的融合抑制剂在治疗HIV中的现状，并回顾了HIV研究领域如何推动其他病毒系统（包括严重急性呼吸综合征（SARS）冠状病毒）中类似疗法的发展。基于肽的融合抑制剂（T20和EK1）已分别针对HIV和冠状病毒开发，其利用1类病毒融合蛋白。这些病毒蛋白的功能和结构同源性促进了潜在的广泛活性治疗。
A number of different viral families have developed convergent methods to infect cells. Class I fusion proteins are commonly used by members of Arenaviridae, Coronaviridae, Filovirdae, Orthomyxoviridae, Paramyxoviridae, and Retroviridae. Class I viral fusion proteins are trimers that are involved in recognizing the cellular receptor, with a region that is responsible for fusing the viral and target cell membranes. During the fusion process, the fusion region folds into a six-helix bundle (6HB) which approximates the two membranes leading to fusion. For human immunodeficiency virus (HIV), the gp41 subunit is responsible for formation of this 6HB. The fusion inhibitor drug enfuvirtide, or T20, is the only US Food and Drug Administration and European Medicines Agency approved drug which targets this crucial step and has been widely used in combination regimens for the treatment of HIV since March 2003. In this review, we describe the current state of peptide-based fusion inhibitors in the treatment of HIV, and review how the field of HIV research is driving advances in development of similar therapeutics in other viral systems, including the severe acute respiratory syndrome (SARS) coronaviruses. Peptide-based fusion inhibitors (T20 and EK1) have been developed for HIV and coronaviruses respectively, that utilize class 1 viral fusion proteins. The functional and structural homology of these viral proteins facilitates potentially broadly active therapies.
DOI：
10.1016/j.bbagen.2005.10.001
发表时间：
2006-01
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Veiga S;Yuan Y;Li X;Santos NC;Liu G;Castanho MA
通讯作者：
Castanho MA