In-depth Bioinformatic Analyses of Human SARS-CoV-2, SARS-CoV, MERS-CoV, and Other Nidovirales Suggest Important Roles of Noncanonical Nucleic Acid Structures in Their Lifecycles

Martin Bartas; Václav Brázda; Natália Bohálová; Alessio Cantara; Adriana Volná; Tereza Stachurová; Katerina Malachová; Eva B. Jagelská; Otília Porubiaková; Jirí Cerven; Petr Pecinka

This is a provisional file, not the final typeset article genomes, but most extensively they have been described in human genomes (Chambers et al., 2015; Bedrat et al., 2016; Hänsel-Hertsch et al., 2016) . They are present also in viruses (Lavezzo et al., 2018; Frasson et al., 2019) . G-quadruplexes probably play an important role in regulating replication in most viral nucleic acids (Lavezzo et al., 2018) , and these structures have been suggested as targets for antiviral therapy (Métifiot et al., 2014; Ruggiero and Richter, 2018) . Along with cruciforms and hairpins, which can be formed in nucleic acids by inverted repeats (IRs), G-quadruplexes are significant genome elements playing specific biological roles. They are involved, for example, in the regulation of DNA replication and transcription (Bagga et al., 1990; Limanskaya, 2009; . It has been demonstrated that IRs are important for various processes in viruses, including their genome organization (Li and Li, 2010; Ishimaru et al., 2013; Xie et al., 2017; Bridges et al., 2019) . Another interesting RNA motif that has been used as a drug target and was found in SARS-CoV targeted by 1,4-diazepame is the "slippery sequence" followed by a pseudoknot (Plant et al., 2005) . This structure, common among all coronaviruses, works based on ribosomal −1 frameshifting that switches on viral fusion proteins (Plant et al., 2005) .