Abstract
The ongoing COVID-19 pandemic highlights the necessity for a more fundamental understanding of the coronavirus life cycle. The causative agent of the disease, SARS-CoV-2, is being studied extensively from a structural standpoint in order to gain insight into key molecular mechanisms required for its survival. Contained within the untranslated regions of the SARS-CoV-2 genome are various conserved stem-loop elements that are believed to function in RNA replication, viral protein translation, and discontinuous transcription. While the majority of these regions are variable in sequence, a 41-nucleotide s2m element within the genome 3′ untranslated region is highly conserved among coronaviruses and three other viral families. In this study, we demonstrate that the SARS-CoV-2 s2m element dimerizes by forming an intermediate homodimeric kissing complex structure that is subsequently converted to a thermodynamically stable duplex conformation. This process is aided by the viral nucleocapsid protein, potentially indicating a role in mediating genome dimerization. Furthermore, we demonstrate that the s2m element interacts with multiple copies of host cellular microRNA (miRNA) 1307-3p. Taken together, our results highlight the potential significance of the dimer structures formed by the s2m element in key biological processes and implicate the motif as a possible therapeutic drug target for COVID-19 and other coronavirus-related diseases.
【초록키워드】 COVID-19, Structure, SARS-CoV-2, coronavirus, Diseases, translation, COVID-19 pandemic, Genome, microRNA, miRNA, molecular mechanism, RNA, Replication, Protein, Region, survival, SARS-CoV-2 genome, discontinuous transcription, cellular, life cycle, causative agent, untranslated region, Viral protein, complex, sequence, viral nucleocapsid protein, element, motif, while, Host, highlight, conserved, the disease, required, majority, interact, biological processe, the viral nucleocapsid, homodimeric, the SARS-CoV-2, the SARS-CoV-2 genome, therapeutic drug, 【제목키워드】 SARS-CoV-2, complex, Host, conserved, interact,