SARS-CoV-2, a novel coronavirus causing overwhelming death and infection worldwide, has emerged as a pandemic. Compared to its predecessor SARS-CoV, SARS-CoV-2 is more infective for being highly contagious and exhibiting tighter binding with host angiotensin-converting enzyme 2 (hACE-2). The entry of the virus into host cells is mediated by the interaction of its spike protein with hACE-2. Thus, a peptide that has a resemblance to hACE-2 but can overpower the spike protein–hACE-2 interaction will be a potential therapeutic to contain this virus. The non-interacting residues in the receptor-binding domain of hACE-2 have been mutated to generate a library of 136 new peptides. Out of this library, docking and virtual screening discover seven peptides that can exert a stronger interaction with the spike protein than hACE-2. A peptide derived from simultaneous mutation of all the non-interacting residues of hACE-2 yields almost three-fold stronger interaction than hACE-2 and thus turns out here to be the best peptide inhibitor of the novel coronavirus. The binding of the best peptide inhibitor with the spike protein is explored further by molecular dynamics, free energy, and principal component analysis, which demonstrate its efficacy compared to hACE-2. The delivery of the screened inhibitors with nanocarriers like metal–organic frameworks will be worthy of further consideration to boost their efficacy.

中文翻译：

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用于抑制 SARS-CoV-2 刺突蛋白的 ACE-2 衍生仿生肽

SARS-CoV-2 是一种新型冠状病毒，在世界范围内造成大量死亡和感染，已成为一种大流行病。与其前身 SARS-CoV 相比，SARS-CoV-2 具有更强的传染性，具有高度传染性，并且与宿主血管紧张素转换酶 2 (hACE-2) 的结合更紧密。病毒进入宿主细胞是通过其刺突蛋白与 hACE-2 的相互作用介导的。因此，一种与 hACE-2 相似但可以抑制刺突蛋白与 hACE-2 相互作用的肽将成为遏制该病毒的潜在治疗方法。hACE-2 受体结合域中的非相互作用残基已发生突变，生成 136 个新肽的文库。在这个库中，对接和虚拟筛选发现了 7 种肽，它们可以比 hACE-2 与刺突蛋白产生更强的相互作用。源自 hACE-2 所有非相互作用残基同时突变的肽产生的相互作用几乎是 hACE-2 的三倍，因此被证明是新型冠状病毒的最佳肽抑制剂。通过分子动力学、自由能和主成分分析进一步探索了最佳肽抑制剂与刺突蛋白的结合，证明了其与 hACE-2 相比的功效。使用金属有机框架等纳米载体来传递筛选的抑制剂值得进一步考虑，以提高其功效。