The base order-dependent component of folding energy has revealed a highly conserved region in HIV-1 genomes that associates with RNA structure. This corresponds to a packaging signal that is recognized by the nucleocapsid domain of the Gag polyprotein. Long viewed as a potential HIV-1 "Achilles heel," the signal can be targeted by a new antiviral compound. Although SARS-CoV-2 differs in many respects from HIV-1, the same technology displays regions with a high base order-dependent folding energy component, which are also highly conserved. This indicates structural invariance (SI) sustained by natural selection. While the regions are often also protein-encoding (e.g. NSP3, ORF3a), we suggest that their nucleic acid level functions can be considered potential "Achilles heels" for SARS-CoV-2, perhaps susceptible to therapies like those envisaged for AIDS. The ribosomal frameshifting element scored well, but higher SI scores were obtained in other regions, including those encoding NSP13 and the nucleocapsid (N) protein.

中文翻译：

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SARS-CoV-2的潜在致命弱点是RNA折叠能的基本顺序依赖性成分

折叠能量的基本顺序依赖性成分揭示了HIV-1基因组中与RNA结构相关的高度保守区域。这对应于被Gag多蛋白的核衣壳结构域识别的包装信号。长期以来，这种信号一直被认为是潜在的HIV-1“致命弱点”，这种信号可以被新型抗病毒化合物靶向。尽管SARS-CoV-2在许多方面与HIV-1有所不同，但相同的技术显示的区域具有高度依赖基序的折叠能成分，并且这些区域也高度保守。这表明自然选择可维持结构不变性（SI）。尽管这些区域通常也都编码蛋白质（例如NSP3，ORF3a），但我们建议将其核酸水平功能视为SARS-CoV-2的潜在“致命弱点”，也许容易受到像针对艾滋病设想的疗法的影响。核糖体移码元件得分良好，但在其他区域获得了较高的SI分数，包括编码NSP13和核衣壳（N）蛋白的区域。