ABSTRACT

The SARS-CoV-2, a positive-sense single-stranded RNA Coronavirus, is a global threat to human health. Thus, understanding its life cycle mechanistically would be important to facilitate the design of antiviral drugs. A key aspect of viral progression is the synthesis of viral proteins by the ribosome of the human host. In Coronaviruses, this process is regulated by the viral 5ʹ and 3ʹ untranslated regions (UTRs), but the precise regulatory mechanism has not yet been well understood. In particular, the 5ʹ-UTR of the viral genome is most likely involved in translation initiation of viral proteins. Here, we performed inline probing and RNase V1 probing to establish a model of the secondary structure of SARS-CoV-2 5ʹ-UTR. We found that the 5ʹ-UTR contains stable structures including a very stable four-way junction close to the AUG start codon. Sequence alignment analysis of SARS-CoV-2 variants 5ʹ-UTRs revealed a highly conserved structure with few co-variations that confirmed our secondary structure model based on probing experiments.

抽象的

SARS-CoV-2是一种正向单链RNA冠状病毒，对人类健康构成全球性威胁。因此，机械地了解其生命周期对于促进抗病毒药物的设计很重要。病毒进程的关键方面是人类宿主的核糖体合成病毒蛋白。在冠状病毒中，此过程受病毒5'和3'非翻译区（UTR）调控，但确切的调控机制尚未得到很好的理解。特别地，病毒基因组的5′-UTR最有可能参与病毒蛋白质的翻译起始。在这里，我们进行了在线探测和RNase V1探测，以建立SARS-CoV-2 5′-UTR二级结构的模型。我们发现5′-UTR包含稳定的结构，包括靠近AUG起始密码子的非常稳定的四向结。