Non-canonical nucleic acid structures play important roles in the regulation of molecular processes. Considering the importance of the ongoing coronavirus crisis, we decided to evaluate genomes of all coronaviruses sequenced to date (stated more broadly, the order Nidovirales) to determine if they contain non-canonical nucleic acid structures. We discovered much evidence of putative G-quadruplex sites and even much more of inverted repeats (IRs) loci, which in fact are ubiquitous along the whole genomic sequence and indicate a possible mechanism for genomic RNA packaging. The most notable enrichment of IRs was found inside 5′UTR for IRs of size 12+ nucleotides, and the most notable enrichment of putative quadruplex sites (PQSs) was located before 3′UTR, inside 5′UTR, and before mRNA. This indicates crucial regulatory roles for both IRs and PQSs. Moreover, we found multiple G-quadruplex binding motifs in human proteins having potential for binding of SARS-CoV-2 RNA. Non-canonical nucleic acids structures in Nidovirales and in novel SARS-CoV-2 are therefore promising druggable structures that can be targeted and utilized in the future.

非经典核酸结构在分子过程的调节中发挥着重要作用。考虑到当前冠状病毒危机的重要性，我们决定评估迄今为止测序的所有冠状病毒的基因组（更广泛地说，顺序巢病毒目）以确定它们是否含有非规范核酸结构。我们发现了许多推定的 G-四链体位点的证据，甚至更多的反向重复 (IR) 位点，它们实际上在整个基因组序列中普遍存在，并表明了基因组 RNA 包装的可能机制。对于大小为 12+ 核苷酸的 IR，最显着的 IR 富集位于 5'UTR 内部，而推定四链体位点 (PQS) 最显着的富集位于 3'UTR 之前、5'UTR 内部和 mRNA 之前。这表明 IR 和 PQS 的监管作用至关重要。此外，我们在人类蛋白质中发现了多个 G-四链体结合基序，具有结合 SARS-CoV-2 RNA 的潜力。非典型核酸结构巢病毒目因此，在新型 SARS-CoV-2 中，它们是有前途的可药物结构，可以在未来进行靶向和利用。