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

in Ronidovirineae (0.39), and the lowest was in Coronaviridae (0.10). When grouped and analyzed by host organisms, new information became apparent. The highest mean PQS frequency was in Nidovirales infecting Invertebrates (0.80), then in Nidovirales infecting Vertebrates including Humans (0.38), and the last in Nidovirales infecting Humans (0.06). In pathogenic human coronaviruses, the total PQSs counts were as follow: 4 PQS in SARS-CoV, 0 PQS in MERS-CoV, and 1 PQS in SARS-CoV-2. To test whether the PQS frequency per 1,000 nt in SARS-CoV-2 is significantly greater than in a random sequence, we generated 10 random sequences with length and GC content the same as in SARS-CoV-2. In that test, the mean PQS frequency per 1,000 nt was 0.16 with standard deviation of 0.05. We applied Wilcoxon signed-rank test with continuity correction and the resulting p-value was 0.0028. Thus, the PQS frequency per 1,000 nt in SARS-CoV-2 (0.03) is significantly lower than expected.