Sztuba-Solinska Joanna, Gosavi Devadatta
Department of Biological Sciences, Auburn University, 120 W. Samford Ave, Rouse Life Sciences Building, Auburn, AL 36849, United States.
Postepy Biochem. 2021 Jan 5;66(4):323-335. doi: 10.18388/pb.2020_362. Print 2020 Dec 31.
Coronaviruses are the causative agents of mild to severe respiratory and intestinal infections in humans. They are the largest RNA viruses, which genomes and encoded RNAs are known to fold into the highly-order structures that play essential roles in the viral replication and infectivity cycle. The recent outbreaks of new pathogenic coronaviruses steered researchers’ attention into the possibility of targeting their RNAs directly with novel RNA-specific drugs and therapeutic strategies. In this manuscript, we highlight the recent biochemical and biophysical methodological advancements that yielded more in-depth insight into the structural and functional composition of coronaviruses cis-acting RNA motifs. We discuss the complexity of these RNA regulatory elements, their intermolecular interactions, post-transcriptional regulation, and their potential as druggable targets. We also indicate the location and function of unstructured and highly-conserved regions in coronaviruses RNA genomes representing viable aims for antisense oligonucleotide or CRISPR-based antiviral strategies.
冠状病毒是导致人类从轻度到重度呼吸道和肠道感染的病原体。它们是最大的RNA病毒,已知其基因组和编码的RNA会折叠成高度有序的结构,这些结构在病毒复制和感染周期中起着至关重要的作用。最近新出现的致病性冠状病毒的爆发,促使研究人员将注意力转向直接用新型RNA特异性药物和治疗策略靶向其RNA的可能性。在本手稿中,我们重点介绍了最近的生化和生物物理方法学进展,这些进展使人们对冠状病毒顺式作用RNA基序的结构和功能组成有了更深入的了解。我们讨论了这些RNA调控元件的复杂性、它们的分子间相互作用、转录后调控以及它们作为可药物靶向的潜力。我们还指出了冠状病毒RNA基因组中无结构且高度保守区域的位置和功能,这些区域是基于反义寡核苷酸或CRISPR的抗病毒策略的可行目标。