Evolving ribonucleocapsid assembly/packaging signals in the genomes of the human and animal coronaviruses: targeting, transmission and evolution

Abstract

A world-wide COVID-19 pandemic intensified strongly the studies of molecular mechanisms related to the coronaviruses. The origin of coronaviruses and the risks of human-to-human, animal-to-human, and human-to-animal transmission of coronaviral infections can be understood only on a broader evolutionary level by detailed comparative studies. In this paper, we studied ribonucleocapsid assembly-packaging signals (RNAPS) in the genomes of all seven known pathogenic human coronaviruses, SARS-CoV, SARS-CoV-2, MERS-CoV, HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63 and compared them with RNAPS in the genomes of the related animal coronaviruses including SARS-Bat-CoV, MERS-Camel-CoV, MHV, Bat-CoV MOP1, TGEV, and one of camel alphacoronaviruses. RNAPS in the genomes of coronaviruses were evolved due to weakly specific interactions between genomic RNA and N proteins in helical nucleocapsids. Combining transitional genome mapping and Jaccard correlation coefficients allows us to perform the analysis directly in terms of underlying motifs distributed over the genome. In all coronaviruses RNAPS were distributed quasi-periodically over the genome with the period about 54 nt biased to 57 nt and to 51 nt for the genomes longer and shorter than that of SARS-CoV, respectively. The comparison with the experimentally verified packaging signals for MERS-CoV, MHV, and TGEV proved that the distribution of particular motifs is strongly correlated with the packaging signals. We also found that many motifs were highly conserved in both characters and positioning on the genomes throughout the lineages that make them promising therapeutic targets. The mechanisms of encapsidation can affect the recombination and co-infection as well.

Molecular insight into the specific interactions of the SARS‐Coronavirus‐2 nucleocapsid with RNA and host protein

“…An elegant study employing all four structural proteins to produce viral‐like particles (VLPs) was shown to deliver many transcripts throughout the viral genome (Syed et al, 2021). These findings are consistent with recent theoretical studies that predict multiple packaging signals exist as ~400 nucleic acid repeats (Chechetkin & Lobzin, 2021; Chechetkin & Lobzin, 2022). Although NMR studies that include our own have confirmed that the SARS‐CoV‐2 N protein NTD and flanking regions bind to short RNAs (Dinesh et al, 2020; Redzic et al, 2021), whether the CTD and CTE have similar affinity for short RNAs remains unclear.…”

“…We selected these two additional large RNA fragments based on recent reports that indicate 54 n.a. repeats are present throughout the SARS‐CoV‐2 genome that are proposed to form multiple packaging signals (Chechetkin & Lobzin, 2021; Chechetkin & Lobzin, 2022). Each of these new RNA fragments was designed to have 6 of these repeats and thus, comprised 324 nucleic acids that correspond to the viral genome of n.a.…”

Genome-Wide Study of Colocalization between Genomic Stretches: A Method and Applications to the Regulation of Gene Expression

“…In particular, coarse-graining of various profiles (e.g., AT/GC content, expression profiles, protein binding profiles) results in a set of stretches within which the characteristics exceed some thresholds. Previously, it was shown that the coarse-grained profiles obtained by transitional automorphic mapping of the genome on itself (TAMGI) contain important information about functional regions in viral genomes [ 55 , 56 ]. The colocalization between stretch sets obtained by coarse-graining of profiles can also be treated by the method developed in our paper.…”