RSAD2 (cig-5), also known as viperin (virus inhibitory protein, endoplasmic reticulum associated, interferon inducible), is a member of the radical S-adenosylmethionine (SAM) superfamily of enzymes. Since the discovery of this enzyme more than a decade ago, numerous studies have shown that it exhibits antiviral activity against a wide range of viruses. However, there is no clear picture demonstrating the mechanism by which RSAD2 restricts the replication process of different viruses, largely because there is no direct evidence describing its in vivo enzymatic activity. As a result, a multifunctionality model has emerged. According to this model the mechanism by which RSAD2 restricts replication of different viruses varies and in many cases is not dependent on the radical-SAM chemistry of RSAD2. If the radical-SAM activity of RSAD2 is not required for its antiviral function, the question worth asking is: why does the cellular defence mechanism induce the expression of the radical-SAM enzyme RSAD2, which is metabolically expensive due to the requirement for a [4Fe–4S] cluster and usage of SAM? Here, in contrast to the multifunctionality view, I put forward a unifying model. I postulate that the radical-SAM activity of RSAD2 modulates cellular metabolic pathways essential for viral replication and/or cell proliferation and survival. As a result, its catalytic activity restricts the replication of a wide range of viruses via a common cellular function. This view is based on recent discoveries hinting towards possible substrates of RSAD2, re-evaluation of previous studies regarding the antiviral activity of RSAD2, and accumulating evidence suggesting a role of human RSAD2 in the metabolic reprogramming of cells.

中文翻译：

---

基于自由基 SAM 化学对 RSAD2（毒蛇素）的广谱抗病毒活性的统一看法

RSAD2 (cig-5)，也称为 viperin（病毒抑制蛋白，内质网相关，干扰素诱导型），是自由基S-腺苷甲硫氨酸 (SAM) 酶超家族的成员。自从十多年前发现这种酶以来，大量研究表明它对多种病毒具有抗病毒活性。然而，并没有清晰的图片证明 RSAD2 限制不同病毒复制过程的机制，主要是因为没有直接证据描述其在体内酶活性。因此，多功能模型应运而生。根据该模型，RSAD2 限制不同病毒复制的机制各不相同，并且在许多情况下不依赖于 RSAD2 的自由基-SAM 化学。如果 RSAD2 的自由基 SAM 活性不是其抗病毒功能所必需的，那么值得提出的问题是：为什么细胞防御机制会诱导自由基 SAM 酶 RSAD2 的表达，由于需要 [ 4Fe–4S] 簇和 SAM 的使用？在这里，与多功能性观点相反，我提出了一个统一模型。我假设 RSAD2 的自由基 SAM 活性调节对病毒复制和/或细胞增殖和存活至关重要的细胞代谢途径。其结果，通过共同的细胞功能。这一观点基于最近的发现，暗示了 RSAD2 的可能底物，重新评估了先前关于 RSAD2 抗病毒活性的研究，以及越来越多的证据表明人类 RSAD2 在细胞代谢重编程中的作用。