The COVID-19 pandemic reminds us that in spite of the scientific progress in the past century, there is a lack of general antiviral strategies. In analogy to broad-spectrum antibiotics as antibacterial agents, developing broad spectrum antiviral agents would buy us time for the development of vaccines and treatments for future viral infections. In addition to targeting viral factors, a possible strategy is to understand host immune defense mechanisms and develop methods to boost the antiviral immune response. Here we summarize the role of NAD+-consuming enzymes in the immune defense against viral infections, with the hope that a better understanding of this process could help to develop better antiviral therapeutics targeting these enzymes. These NAD+-consuming enzymes include PARPs, sirtuins, CD38, and SARM1. Among these, the antiviral function of PARPs is particularly important and will be a focus of this review. Interestingly, NAD+ biosynthetic enzymes are also implicated in immune responses. In addition, many viruses, including SARS-CoV-2 contain a macrodomain-containing protein (NSP3 in SARS-CoV-2), which serves to counteract the antiviral function of host PARPs. Therefore, NAD+ and NAD+-consuming enzymes play crucial roles in immune responses against viral infections and detailed mechanistic understandings in the future will likely facilitate the development of general antiviral strategies.

中文翻译：

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在抵抗病毒感染的免疫防御中消耗 NAD+ 的酶

COVID-19 大流行提醒我们，尽管上个世纪科学取得了进步，但仍缺乏通用的抗病毒策略。与作为抗菌剂的广谱抗生素类比，开发广谱抗病毒剂将为我们争取时间来开发疫苗和治疗未来的病毒感染。除了针对病毒因子，一种可能的策略是了解宿主免疫防御机制并开发增强抗病毒免疫反应的方法。在这里，我们总结了消耗 NAD+ 的酶在抵抗病毒感染的免疫防御中的作用，希望更好地了解这一过程有助于开发针对这些酶的更好的抗病毒疗法。这些消耗 NAD+ 的酶包括 PARP、sirtuins、CD38 和 SARM1。在这些当中，PARP 的抗病毒功能尤为重要，将成为本次审查的重点。有趣的是，NAD+ 生物合成酶也与免疫反应有关。此外，包括 SARS-CoV-2 在内的许多病毒都含有一种含有宏结构域的蛋白质（SARS-CoV-2 中的 NSP3），它可以抵消宿主 PARP 的抗病毒功能。因此，NAD+ 和 NAD+ 消耗酶在针对病毒感染的免疫反应中起着至关重要的作用，未来详细的机制理解可能会促进一般抗病毒策略的发展。其作用是抵消宿主 PARP 的抗病毒功能。因此，NAD+ 和 NAD+ 消耗酶在针对病毒感染的免疫反应中起着至关重要的作用，未来详细的机制理解可能会促进一般抗病毒策略的发展。其作用是抵消宿主 PARP 的抗病毒功能。因此，NAD+ 和 NAD+ 消耗酶在针对病毒感染的免疫反应中起着至关重要的作用，未来详细的机制理解可能会促进一般抗病毒策略的发展。