RNA viruses, including the coronavirus, develop a unique strategy to evade the host immune response by interrupting the normal function of cytosolic retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs). RLRs rapidly detect atypical nucleic acids, thereby triggering the antiviral innate immune signaling cascade and subsequently activates the interferons transcription and induction of other proinflammatory cytokines and chemokines. Nonetheless, these receptors are manipulated by viral proteins to subvert the host immune system and sustain the infectivity and replication potential of the virus. RIG-I senses the single-stranded, double-stranded, and short double-stranded RNAs and recognizes the key signature, a 5′-triphosphate moiety, at the blunt end of the viral RNA. Meanwhile, the melanoma differentiation-associated gene 5 (MDA5) is triggered by longer double stranded RNAs, messenger RNAs lacking 2′-O-methylation in their 5′-cap, and RNA aggregates. Therefore, structural insights into the nucleic-acid-sensing and downstream signaling mechanisms of these receptors hold great promise for developing effective antiviral therapeutic interventions. This review highlights the critical roles played by RLRs in viral infections as well as their ligand recognition mechanisms. In addition, we highlight the crosstalk between the toll-like receptors and RLRs and provide a comprehensive overview of RLR-associated diseases as well as the therapeutic potential of RLRs for the development of antiviral-drugs. Moreover, we believe that these RLR-based antivirals will serve as a step toward countering the recent coronavirus disease 2019 pandemic.

中文翻译：

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对 RIG-I 样受体独特的 RNA 识别和治疗潜力的结构洞察

包括冠状病毒在内的 RNA 病毒开发了一种独特的策略，通过中断细胞溶质视黄酸诱导基因 I (RIG-I) 样受体 (RLR) 的正常功能来逃避宿主免疫反应。RLR 可快速检测非典型核酸，从而触发抗病毒先天免疫信号级联反应，随后激活干扰素转录并诱导其他促炎细胞因子和趋化因子。尽管如此，这些受体被病毒蛋白操纵以破坏宿主免疫系统并维持病毒的传染性和复制潜力。RIG-I 感知单链、双链和短双链 RNA，并识别病毒 RNA 平端的关键特征，即 5'-三磷酸部分。同时，5'-帽中的O-甲基化和 RNA 聚集体。因此，对这些受体的核酸传感和下游信号传导机制的结构洞察为开发有效的抗病毒治疗干预提供了广阔的前景。本综述重点介绍了 RLR 在病毒感染中的关键作用及其配体识别机制。此外，我们强调了 toll 样受体和 RLR 之间的串扰，并全面概述了 RLR 相关疾病以及 RLR 在开发抗病毒药物方面的治疗潜力。此外，我们相信这些基于 RLR 的抗病毒药物将成为对抗最近的 2019 年冠状病毒病大流行的一步。