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 the ssRNA genome of length about 30,000 nt by the nucleocapsid would need 4.4 × 10³ 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 nonoverlapping 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. Communicated by Ramaswamy H. Sarma.

Keywords: COVID-19; SARS-CoV; SARS-CoV-2; genome packaging; helical nucleocapsid.

Figure 1.

The plots for the normalized NCF deviations defined by Equations (26) and (27). The initial ranges of plots shown in the inserts were re-calculated by replacing the highest Fourier harmonics by the peaks defined by extreme value statistics in the DFT spectra. The characteristic spacings m₀ are explicitly marked by the arrows. The horizontal lines correspond to the significance Pr = 0.05 for the reshuffled random sequences. The panels A–D correspond to the nucleotides of particular types in the genome of SARS-CoV (accession NC_004718).

Figure 2.

The plots for the normalized NCF deviations defined by Equations (26) and (27). The initial ranges of plots shown in the inserts were re-calculated by replacing the highest Fourier harmonics by the peaks defined by extreme value statistics in the DFT spectra. The characteristic spacings m₀ are explicitly marked by the arrows. The horizontal lines correspond to the significance Pr = 0.05 for the reshuffled random sequences. The panels A–D correspond to the nucleotides of particular types in the genome of SARS-CoV-2 (accession MT371037).

Figure 3.

The correlograms obtained by averaging of the normalized NCF deviations defined by Equations (24), (26) and (27) calculated within nonoverlapping windows of width 432 nt for the genomes of NC_004718 (A), MT371038 (B), MT295464 (C) and MT371037 (D). The horizontal lines correspond to the significance Pr = 0.05.

Figure 4.

The DDFT spectra of the periodograms obtained by averaging of the DFT spectra defined by Equations (4) and (7) calculated within nonoverlapping windows of width 432 nt for the genomes of NC_004718 (A), MT371038 (B), MT295464 (C) and MT371037 (D). The horizontal lines correspond to the significance Pr = 0.05.

Figure 5.

The profiles of the normalized NCF deviations defined by Equations (24), (26) and (27) for the components with m₀ = 54 (A), 84 (B) and 87 (C) calculated within nonoverlapping windows of width 432 nt for the genomes of NC_004718, MT371038, MT295464 and MT371037. The horizontal lines correspond to the significance Pr = 0.05.

Figure 6.

The profiles of the total numbers of nucleotides after TAMGI with steps s = 54 (A), 84 (B) and 87 (C) within nonoverlapping windows of width 432 nt for the genomes of NC_004718, MT371038, MT295464 and MT371037.