Ribonucleocapsid assembly/packaging signals in the genomes of the coronaviruses SARS-CoV and SARS-CoV-2: detection, comparison and implications for therapeutic targeting

Abstract

The genomic ssRNA of coronaviruses is packaged within a helical nucleocapsid. Due to transitional symmetry of a helix, weakly specific cooperative interaction between ssRNA and nucleocapsid proteins leads to the natural selection of specific quasi-periodic assembly/packaging signals in the related genomic sequence. Such signals coordinated with the nucleocapsid helical structure were detected and reconstructed in the genomes of the coronaviruses SARS-CoV and SARS-CoV-2. The main period of the signals for both viruses was about 54 nt, that implies 6.75 nt per N protein. The complete coverage of ssRNA genome of length about 30,000 nt by the nucleocapsid would need 4,400 N proteins, that makes them the most abundant among the structural proteins. The repertoires of motifs for SARS-CoV and SARS-CoV-2 were divergent but nearly coincided for different isolates of SARS-CoV-2. We obtained the distributions of assembly/packaging signals over the genomes with non-overlapping windows of width 432 nt. Finally, using the spectral entropy, we compared the load from point mutations and indels during virus age for SARS-CoV and SARS-CoV-2. We found the higher mutational load on SARS-CoV. In this sense, SARS-CoV-2 can be treated as a "newborn" virus. These observations may be helpful in practical medical applications and are of basic interest.

Unpacking Pandora from Its Box: Deciphering the Molecular Basis of the SARS-CoV-2 Coronavirus

“…The primary role of the N protein is to package the viral genome into long, flexible, helical ribonucleoprotein (RNP) complexes [ 86 ]. Weak specific interaction between the single stranded RNA and N proteins relies on packaging signals of 2–4 bps throughout the SARS-CoV-2 genome [ 87 ]. It is believed that longer motifs for packaging would be too restrictive due to the protein coding function of the SARS-CoV-2 genome [ 87 ].…”

“…Weak specific interaction between the single stranded RNA and N proteins relies on packaging signals of 2–4 bps throughout the SARS-CoV-2 genome [ 87 ]. It is believed that longer motifs for packaging would be too restrictive due to the protein coding function of the SARS-CoV-2 genome [ 87 ]. Nevertheless, a long packaging motif (UAUUCAAACAAUUGUUG) has been identified in isolates of this novel coronavirus [ 87 ].…”

“…It is believed that longer motifs for packaging would be too restrictive due to the protein coding function of the SARS-CoV-2 genome [ 87 ]. Nevertheless, a long packaging motif (UAUUCAAACAAUUGUUG) has been identified in isolates of this novel coronavirus [ 87 ]. Considering the variable nature of the spike protein, N should also be considered a more promising therapeutic target as it is more stable against point mutation load [ 87 ].…”

“…Nevertheless, a long packaging motif (UAUUCAAACAAUUGUUG) has been identified in isolates of this novel coronavirus [ 87 ]. Considering the variable nature of the spike protein, N should also be considered a more promising therapeutic target as it is more stable against point mutation load [ 87 ]. The SARS-CoV-2 nucleocapsid protein shares approximately 90% amino acid identity with that of SARS-CoV [ 84 ].…”

Combining detection and reconstruction of correlational and periodic motifs in viral genomic sequences with transitional genome mapping: Application to COVID-19

“…The method of TAMGI was sketched briefly in our paper [19] when applying to the study of ribonucleocapsid assembly/packaging signals in the genomes of the severe acute respiratory syndrome coronaviruses SARS-CoV and SARS-CoV-2. In this publication we develop the extended theory and derive the relevant statistical criteria for analysis of the output set of patterns in TAMGI.…”