National Center for Biotechnology, King Abdulaziz City for Science and Technology, Riyadh 11442, Saudi Arabia.
Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd, MDC07, Tampa, FL 33612, USA.
Viruses. 2021 Feb 22;13(2):339. doi: 10.3390/v13020339.
Middle East respiratory syndrome is a severe respiratory illness caused by an infectious coronavirus. This virus is associated with a high mortality rate, but there is as of yet no effective vaccine or antibody available for human immunity/treatment. Drug design relies on understanding the 3D structures of viral proteins; however, arriving at such understanding is difficult for intrinsically disordered proteins, whose disorder-dependent functions are key to the virus's biology. Disorder is suggested to provide viral proteins with highly flexible structures and diverse functions that are utilized when invading host organisms and adjusting to new habitats. To date, the functional roles of intrinsically disordered proteins in the mechanisms of MERS-CoV pathogenesis, transmission, and treatment remain unclear. In this study, we performed structural analysis to evaluate the abundance of intrinsic disorder in the MERS-CoV proteome and in individual proteins derived from the MERS-CoV genome. Moreover, we detected disordered protein binding regions, namely, molecular recognition features and short linear motifs. Studying disordered proteins/regions in MERS-CoV could contribute to unlocking the complex riddles of viral infection, exploitation strategies, and drug development approaches in the near future by making it possible to target these important (yet challenging) unstructured regions.
中东呼吸综合征是一种由传染性冠状病毒引起的严重呼吸系统疾病。这种病毒的死亡率很高，但目前还没有针对人类免疫/治疗的有效疫苗或抗体。药物设计依赖于对病毒蛋白 3D 结构的理解；然而，对于固有无序蛋白来说，理解这一点很困难，因为它们的无序依赖功能是病毒生物学的关键。无序被认为为病毒蛋白提供了高度灵活的结构和多样化的功能，这些功能在入侵宿主生物和适应新栖息地时被利用。迄今为止，固有无序蛋白在 MERS-CoV 发病机制、传播和治疗中的功能作用尚不清楚。在这项研究中，我们进行了结构分析，以评估 MERS-CoV 蛋白质组和源自 MERS-CoV 基因组的个别蛋白质中固有无序的丰度。此外，我们还检测了无序蛋白结合区域，即分子识别特征和短线性基序。研究 MERS-CoV 中的无序蛋白/区域可以通过靶向这些重要（但具有挑战性）的无结构区域，有助于在不久的将来解开病毒感染、利用策略和药物开发方法的复杂难题。
