School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
Department of Immunology, Zanjan University of Medical Sciences, Zanjan, Iran.
Immunopharmacol Immunotoxicol. 2023 Dec;45(6):639-649. doi: 10.1080/08923973.2023.2215405. Epub 2023 Jun 19.
The emerging pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has imposed significant mortality and morbidity on the world. An appropriate immune response is necessary to inhibit SARS-CoV-2 spread throughout the body.
During the early stages of infection, the pathway of stimulators of interferon genes (STING), known as the cGAS-STING pathway, has a significant role in the induction of the antiviral immune response by regulating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Interferon regulatory factor 3 (IRF3), two key pathways responsible for proinflammatory cytokines and type I IFN secretion, respectively.
During the late stages of COVID-19, the uncontrolled inflammatory responses, also known as cytokine storm, lead to the progression of the disease and poor prognosis. Hyperactivity of STING, leading to elevated titers of proinflammatory cytokines, including Interleukin-I (IL-1), IL-4, IL-6, IL-18, and tissue necrosis factor-α (TNF-α), is considered one of the primary mechanisms contributing to the cytokine storm in COVID-19.
Exploring the underlying molecular processes involved in dysregulated inflammation can bring up novel anti-COVID-19 therapeutic options. In this article, we aim to discuss the role and current studies targeting the cGAS/STING signaling pathway in both early and late stages of COVID-19 and COVID-19-related complications and the therapeutic potential of STING agonists/antagonists. Furthermore, STING agonists have been discussed as a vaccine adjuvant to induce a potent and persistent immune response.
由严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）引起的 2019 年冠状病毒病（COVID-19）大流行，给全球带来了巨大的病死率和发病率。适当的免疫反应对于抑制 SARS-CoV-2 在全身的传播是必要的。
在感染的早期阶段，干扰素基因刺激物（STING）途径，即 cGAS-STING 途径，通过调节核因子 kappa 轻链增强子的活化 B 细胞（NF-κB）和干扰素调节因子 3（IRF3），在诱导抗病毒免疫反应方面发挥着重要作用，这两个关键途径分别负责促炎细胞因子和 I 型干扰素的分泌。
在 COVID-19 的晚期，失控的炎症反应，也称为细胞因子风暴，导致疾病的进展和不良预后。STING 的过度活跃，导致促炎细胞因子（包括白细胞介素-1（IL-1）、IL-4、IL-6、IL-18 和肿瘤坏死因子-α（TNF-α））的滴度升高，被认为是 COVID-19 中细胞因子风暴的主要机制之一。
探索失调的炎症所涉及的潜在分子过程，可以为抗 COVID-19 治疗提供新的选择。本文旨在讨论 cGAS/STING 信号通路在 COVID-19 早期和晚期以及 COVID-19 相关并发症中的作用和当前研究，并讨论 STING 激动剂/拮抗剂的治疗潜力。此外，还讨论了 STING 激动剂作为疫苗佐剂诱导强烈和持久免疫反应的潜力。
