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. 2020 Oct 20:2020:7234961.
doi: 10.1155/2020/7234961. eCollection 2020.

Sequence Analysis and Structure Prediction of SARS-CoV-2 Accessory Proteins 9b and ORF14: Evolutionary Analysis Indicates Close Relatedness to Bat Coronavirus

Chittaranjan Baruah  1 , Papari Devi  2 , Dhirendra K Sharma  3
Affiliations

Sequence Analysis and Structure Prediction of SARS-CoV-2 Accessory Proteins 9b and ORF14: Evolutionary Analysis Indicates Close Relatedness to Bat Coronavirus

Chittaranjan Baruah et al. Biomed Res Int. .

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a single-stranded RNA genome that encodes 14 open reading frames (ORFs), eight of which encode accessory proteins that allow the virus to infect the host and promote virulence. The genome expresses around 29 structural and nonstructural protein products. The accessory proteins of SARS-CoV-2 are not essential for virus replication but do affect viral release, stability, and pathogenesis and finally contribute to virulence. This paper has attempted the structure prediction and functional analysis of two such accessory proteins, 9b and ORF14, in the absence of experimental structures. Sequence analysis, structure prediction, functional characterization, and evolutionary analysis based on the UniProtKB reviewed the amino acid sequences of SARS-CoV-2 9b (P0DTD2) and ORF14 (P0DTD3) proteins. Modeling has been presented with the introduction of hybrid comparative and ab initio modeling. QMEANDisCo 4.0.0 and ProQ3 for global and local (per residue) quality estimates verified the structures as high quality, which may be attributed to structure-based drug design targets. Tunnel analysis revealed the presence of 1-2 highly active tunneling sites, perhaps which will able to provide certain inputs for advanced structure-based drug design or to formulate potential vaccines in the absence of a complete experimental structure. The evolutionary analysis of both proteins of human SARS-CoV-2 indicates close relatedness to the bat coronavirus. The whole-genome phylogeny indicates that only the new bat coronavirus followed by pangolin coronaviruses has a close evolutionary relationship with the novel SARS-CoV-2.

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Conflict of interest statement

The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
A conceptual framework of the present study for analysis of SARS-CoV-2 accessory proteins ORF9b and ORF14.
Figure 2
Figure 2
Amino acid composition of SARS-CoV-2 9b protein (leucine and valine-rich).
Figure 3
Figure 3
Amino acid composition of SARS-CoV-2 ORF14 protein (leucine and valine-rich).
Figure 4
Figure 4
Structure of SARS-CoV-2 9b protein along with major active sites.
Figure 5
Figure 5
Structure of SARS-CoV-2 9b protein and its two high-throughput tunnels. Tunnels are colored on the basis of preferences in throughput values, i.e., tunnel-1 (blue) and tunnel-2 (green). The high relevance pocket is shown (yellow).
Figure 6
Figure 6
Structure of SARS-CoV-2 ORF14 protein along with major active sites.
Figure 7
Figure 7
Structure of SARS-CoV-2 ORF14 protein along with its throughput tunnels (blue).
Figure 8
Figure 8
Protein family membership of SARS-CoV-2 protein 9b resembles the SARS-like protein (IPR018542) and the 9b SARS InterPro homologous superfamily (9-97; IPR037223).
Figure 9
Figure 9
Protein family membership of SARS-CoV-2 protein 14 resembles SARS-like protein (IPR035113). The protein is with three domains: (i) noncytoplasmic domain (1-51), (ii) transmembrane region (52-72), and (iii) cytoplasmic domain (73-73).
Figure 10
Figure 10
Evolutionary analysis of 9b protein of SARS-CoV-2 by Maximum Likelihood method and JTT matrix-based model (Jones and Taylor, 1992). The tree with the highest log likelihood (-1113.75) is shown. This analysis involved 9 amino acid sequences. There were a total of 141 positions in the final dataset. Evolutionary analyses were conducted in MEGA X.
Figure 11
Figure 11
Evolutionary analysis of ORF14 protein of SARS-CoV-2 by Maximum Likelihood method and JTT matrix-based model (Jones and Taylor, 1992). The tree with the highest log likelihood (-497.56) is shown. The percentage of trees, in which the associated taxa clustered together, is shown next to the branches. This analysis involved 14 amino acid sequences. There were a total of 73 positions in the final dataset. Evolutionary analyses were conducted in MEGA X.
Figure 12
Figure 12
Evolutionary relationships of different coronaviruses based on whole-genome bootstrap phylogenetic analysis (ML tree).
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