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

Abstract

Noncanonical nucleic acid structures play important roles in the regulation of molecular processess. Considering the importance of the ongoing coronavirus crisis, we decided to evaluate genomes of all coronaviruses sequences to date (stated more broadly, the order Nidovirales) to determine if they contain noncanonical nucleic acid structures. We discovered much evidence of the 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 if IRs was found inside 5UTR for IRs of size 12+ nucleotides, and the most notable enrichment of putative quadruplex sites (PQSs) was located befor 3UTR, inside 5UTR, 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. Noncanonical nucleic acids structures in Nidoviralesand in novel SARS-CoV-2 are therefore promising druggable structures that can be targeted and utilized in the future.Noncanonical nucleic acid structures play important roles in the regulation of molecular processess. Considering the importance of the ongoing coronavirus crisis, we decided to evaluate genomes of all coronaviruses sequences to date (stated more broadly, the order Nidovirales) to determine if they contain noncanonical nucleic acid structures. We discovered much evidence of the 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 if IRs was found inside 5UTR for IRs of size 12+ nucleotides, and the most notable enrichment of putative quadruplex sites (PQSs) was located befor 3UTR, inside 5UTR, 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. Noncanonical nucleic acids structures in Nidoviralesand in novel SARS-CoV-2 are therefore promising druggable structures that can be targeted and utilized in the future.