The emergence of 2019 novel coronavirus (2019-nCoV) is of global concern and might have emerged from RNA recombination among existing coronaviruses. CoV spike (S) protein which is crucial for receptor binding, membrane fusion via conformational changes, internalization of the virus, host tissue tropism and comprises crucial targets for vaccine development, remain largely uncharacterized. Therefore, the present study has been planned to determine the sequence variation, structural and antigenic divergence of S glycoprotein which may be helpful for the management of 2019-nCoV infection. The sequences of spike glycoprotein of 2019-nCoV and SARS coronavirus (SARS-CoV) were used for the comparison. The sequence variations were determined using EMBOSS Needle pairwise sequence alignment tools.
Our phylogenetic analysis revealed that a 2019-nCoV arises from the predecessors strains of SARS-coronaviruses. In the present study, we have shown the sequence divergence, differences and similarity in the glycosylation sites and antigenic variation in spike glycoprotein of 2019-nCoV and compared with the SARS-CoV strain. Our amino acid sequence alignment data suggests a significant variation of 12.8%. In addition, we have found 23.6% difference in minimal receptor-binding domain of S glycoprotein. The significant variation in minimal receptor binding domain of S-glycoprotein suggests that 2019-nCoV may have alteration in virus binding capacity and infectivity into the host cell receptor. We have found novel glycosylation sites in the spike glycoprotein of 2019-nCoV suggesting that virus may utilize different glycosylation to interact with its receptors.
We have also found that the glycosylation sites in minimal receptor-binding domain exhibits similar sites to other coronaviruses. While comparing the antigenic sites, we have found that 2019-nCoV exhibits novel CTL epitopes that may results in distinct antigenic response as compared to SARS coronavirus. These novel CTL epitopes may impart opportunities for the development of peptide based vaccine for the prevention of 2019-nCoV. However, some of the epitopes were found to be similar in both the glycoproteins, suggesting that SARS-associated peptide based vaccine might be used for the prevention of 2019-nCoV in the current scenario. In this regard we have found one of the CTL epitope RVDFCGKGY has been used to design peptide based vaccine for SARS-CoV and was found to be effective in various animal models . Furthermore, we have found insignificant structural divergence between two glycoproteins which suggests that the attachment inhibitors designed for SARS-CoV may be used as the current choice of therapy for 2019-nCoV. Variation in amino acid sequences and distinctive antigenicity of 2019-nCoV suggests that although the current virus infection is not severe, it has a potential to become pandemic. Moreover, we identified an insignificant structural divergence in the spike glycoproteins that suggests that although the virus has changed its sequence its structure remains the same. The data also suggests the scope of coronavirus specific attachment inhibitors as the choice of therapy in the current pandemic situation.
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