3.1 Minor Differences in Protein Homology of SARS-CoV and 2019-nCoV
There are no major, but Minor differences within the structure of homologous S glycoprotein, M glycoprotein, E protein and N phosphoprotein of SARS-CoV and 2019-nCoV (Figure 1). The filled 3d-structures shows different exposure pattern, implying that sequences of 2019-nCoV viral proteins directly affect on 3D-structure and surface exposure pattern. This result establishes evolution of 2019-nCoV proteome being potentially able to lead to the different behavioral pattern, comparing to SARS-CoV. Minor differences in dots of Ramachandran plots confirm minor, but not major, structural homologous variation of SARS-CoV and 2019-nCoV.
Additionally, comparison of modeled proteins with Non-redundant set of PBD structure (figure 1-b) confirms the comparative results.
3.3 Difference in Proteasomal Cleavage Pattern and MHC Class I Presentation of T-cells Epitopes of 2019-nCoV and SARS-CoV
The IEDB analysis showed that the proteasomal cleavage pattern of 9-meric peptides of 2019-nCoV and SARS-CoV are different. The top-ten 9-mer peptides of each viral protein were compared via “total score” index. The S glycoprotein of 2019-nCoV has 26.57% less efficiency in antigen proteasomal cleavage and presentation to MHC class I, compared to SARS-CoV S glycoprotein. Also, the other giant surface-exposed protein, M protein of 2019-nCoV, has 20.59% less efficiency in proteasomal cleavage and presentation to MHC class I compared to SARS-CoV M glycoprotein. (Table 1)
Despite above proteins, the E protein and N phosphoprotein of 2019-nCoV and SARS-CoV show the different pattern in antigen proteasomal cleavage and presentation to MHC class I. There is 0.08% more efficiency in the cleavage of E protein of SARS-CoV and its presentation to MHC class I, compared to 2019-nCoV. Also, proteasomal cleavage and MHC class I presentation of N phosphoprotein of SARS-CoV done 15.19% more efficient, compared to 2019-nCoV.
As our results show, “LTDEMIAQY” (total score: 1.71, PPC: 0.0423), “CVADYSVLY” (total score: 1.16, PPC: 0.2654) and “TSNQVAVLY” (total score: 0.94, PPC: 0.2724) are top-three hotspot 9-meric presented peptides in S glycoprotein of 2019-nCoV. In addition, “ATSRTLSYY” (total score: 0.92, PPC: 0.0159) are “YANRNRFLY” (total score: 0.51, PPC: 0.0140) are top-two hotspot 9-meric presented peptides in M glycoprotein of 2019-nCoV.
3.2 Difference in B-cells Epitopes of 2019-nCoV and SARS-CoV
The results of prediction of potential B-cells epitopes via BepiPred V2.0 show that S glycoprotein and M glycoprotein of 2019-nCoV contain higher-potent B-cell epitopes than SARS-CoV, while E protein and N phosphoprotein of SARS-CoV contain higher-potent B-cell epitopes than 2019-nCoV. (Figure 2) Also, SWISS-MODEL results of structure prediction approved that the predicted epitopes have surface exposure.
3.3 Differences in Anti-inflammatory Properties of 2019-nCOV and SARS-COV Epitopes
The Protein scan of four major viral proteins of 2019-nCoV and SARS-COV, e.g. S glycoprotein, M glycoprotein, E protein and N phosphoprotein proteins, show that the 9-meric epitopes of 2019-nCOV have higher anti-inflammatory properties in S glycoprotein (264 9-meric epitopes in 2019-nCOV [Top-ten mean score = 4.50 ± 0.10] , comparing 77 9-meric epitopes in SARS-CoV [Top-ten mean score = 4.34 ± 0.36] ) and N phosphoprotein (224 9-meric epitopes in 2019-nCOV, comparing 54 9-meric epitopes in SARS-CoV). Despite two above proteins, analysis of the anti-inflammatory property of the 9-meric M glycoprotein epitopes in 2019-nCOV and SARS-COV shows that this protein has the slightly more anti-inflammatory property SARS-CoV (29 9-meric anti-inflammatory epitopes), comparing 2019-nCoV (23 9-meric anti-inflammatory epitopes). The analysis of E protein in these two viruses also showed the same result (7 9-meric anti-inflammatory epitopes). (Table 2)