Department of Biochemistry, German University in Cairo, New Cairo, Egypt.
Department of Microbiology and Immunology, German University in Cairo, New Cairo, Egypt.
Int J Biochem Cell Biol. 2022 Apr;145:106185. doi: 10.1016/j.biocel.2022.106185. Epub 2022 Feb 24.
Viroporins are indispensable for viral replication. As intracellular ion channels they disturb pH gradients of organelles and allow Ca flux across ER membranes. Viroporins interact with numerous intracellular proteins and pathways and can trigger inflammatory responses. Thus, they are relevant targets in the search for antiviral drugs. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) underlies the world-wide pandemic of COVID-19, where an effective therapy is still lacking despite impressive progress in the development of vaccines and vaccination campaigns. Among the 29 proteins of SARS-CoV-2, the E- and ORF3a proteins have been identified as viroporins that contribute to the massive release of inflammatory cytokines observed in COVID-19. Here, we describe structure and function of viroporins and their role in inflammasome activation and cellular processes during the virus replication cycle. Techniques to study viroporin function are presented, with a focus on cellular and electrophysiological assays. Contributions of SARS-CoV-2 viroporins to the viral life cycle are discussed with respect to their structure, channel function, binding partners, and their role in viral infection and virus replication. Viroporin sequences of new variants of concern (α-ο) of SARS-CoV-2 are briefly reviewed as they harbour changes in E and 3a proteins that may affect their function.
病毒离子通道蛋白对于病毒复制是不可或缺的。作为细胞内离子通道，它们会扰乱细胞器的 pH 梯度，并允许 Ca2+ 通过内质网膜流动。病毒离子通道蛋白与许多细胞内蛋白和途径相互作用，并能引发炎症反应。因此，它们是寻找抗病毒药物的相关靶点。引发 COVID-19 大流行的严重急性呼吸综合征冠状病毒 2 型（SARS-CoV-2），尽管疫苗和接种运动的发展取得了令人瞩目的进展，但仍缺乏有效的治疗方法。在 SARS-CoV-2 的 29 种蛋白中，E 蛋白和 ORF3a 蛋白已被确定为病毒离子通道蛋白，它们有助于 COVID-19 中观察到的大量炎症细胞因子的释放。在这里，我们描述了病毒离子通道蛋白的结构和功能，以及它们在炎症小体激活和病毒复制周期中细胞过程中的作用。介绍了研究病毒离子通道蛋白功能的技术，重点是细胞和电生理测定。还讨论了 SARS-CoV-2 病毒离子通道蛋白对病毒生命周期的贡献，包括它们的结构、通道功能、结合伙伴，以及它们在病毒感染和病毒复制中的作用。简要回顾了 SARS-CoV-2 的新型关注变体（α-ο）的病毒离子通道蛋白序列，因为它们在 E 和 3a 蛋白中发生了可能影响其功能的变化。
