Membrane fusion is an integral part of the viral infection. The fusion between an enveloped virus and a host cell is the first step for viral infection. It has been a long-standing effort to develop anti-viral therapies involving inhibitors that block the fusion between virus and host cell. However, these inhibitors are highly specific against a particular virus. Development of generic inhibitors is extremely essential in the current scenario to overcome emerging and re-emerging contagious diseases that cause millions of fatalities every year. In this work, we have studied the effect of three different peptides derived from a phagosomal protein coronin 1. Coronin 1 is being recruited at the phagosomal membrane of Mycobacterium infected host cells and is implicated in preventing lysosomal fusion. Interestingly, coronin 1 contains tryptophan-aspartic acid repeats, which are conserved across species. In order to understand the mechanistic basis of coronin 1 function, we designed peptides that contain conserved tryptophan-aspartic acid region, and evaluated their membrane binding, effect on membrane fusion, depth-dependent membrane ordering and water penetration into the membrane. Our results demonstrate that these peptides exclusively bind to membranes in presence of negatively charged lipids and do not influence lipid mixing. However, two peptides, TG-23 and GL-22, substantially reduce the extent of content mixing. The reduction in content mixing in presence of TG-23 and GL-22 could be interpreted in terms of their inhibitory effect on water penetration into the membrane. We envisage that these results will contribute to the development of the generic peptide-based membrane fusion inhibitors.

膜融合是病毒感染的一个组成部分。包膜病毒与宿主细胞的融合是病毒感染的第一步。开发抗病毒疗法是一项长期的努力，其中涉及阻断病毒与宿主细胞融合的抑制剂。然而，这些抑制剂对特定病毒具有高度特异性。在当前情况下，开发通用抑制剂对于克服每年导致数百万人死亡的新出现和重新出现的传染病至关重要。在这项工作中，我们研究了源自吞噬体蛋白 coronin 1 的三种不同肽的作用。Coronin 1 正在分枝杆菌的吞噬体膜上被募集受感染的宿主细胞并参与阻止溶酶体融合。有趣的是，coronin 1 包含色氨酸-天冬氨酸重复序列，这些重复序列在物种间是保守的。为了了解coronin 1功能的机制基础，我们设计了含有保守色氨酸-天冬氨酸区域的肽，并评估了它们的膜结合、对膜融合的影响、深度依赖性膜排序和水对膜的渗透。我们的结果表明，这些肽在存在带负电荷的脂质时仅与膜结合，并且不影响脂质混合。然而，两种肽 TG-23 和 GL-22 显着降低了内容物混合的程度。在 TG-23 和 GL-22 存在下含量混合的减少可以解释为它们对水渗透到膜中的抑制作用。