Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design

Jacob Kames; David Dillon Holcomb; Ofer Kimchi; Michael DiCuccio; Nobuko Hamasaki-Katagiri; Tony Wang; Anton A Komar; Aikaterini Alexaki; Chava Kimchi-Sarfaty

RNA structures were predicted using two distinct secondary structure prediction algorithms [28] [29] [30] . Of the top 10 coronaviruses whose predicted minimum free energy (MFE) structures best aligned to that of SARS-CoV-2, seven matched among the two algorithms, showing a high degree of agreement among the two sets of structure predictions. Those seven consensus best-aligned structures are shown, alongside the novel coronavirus post-frameshift structure, in Figure The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.30.016832 doi: bioRxiv preprint Finally, we used our recently published RNA landscape enumeration algorithm [29] to study the RNA folding beyond the MFE structures. We find that even those coronaviruses whose MFE structure does not contain a pseudoknot will fold into a pseudoknot in a relatively high fraction of cases, and that most coronaviruses have a relatively high probability of the initial stem following the frameshift folding into part of a 3-stem pseudoknot like the one exhibited by the SARS-CoV-2 MFE structure (Figure 4 I) .