Structural, glycosylation and antigenic variation between 2019 novel coronavirus (2019-nCoV) and SARS coronavirus (SARS-CoV)

Abstract

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. The variation in glycosylation sites was predicted by NetNGlyc 1.0 and validated by N-GlyDE server. Antigenicity was predicted by NetCTL 1.2 and validated by IEDB Analysis Resource server. The structural divergence was determined by using SuperPose Version 1.0 based on cryo-EM structure of the SARS coronavirus spike glycoprotein. Our data suggests that 2019-nCoV is newly spilled coronavirus into humans in China is closely related to SARS-CoV, which has only 12.8% of difference with SARS-CoV in S protein and has 83.9% similarity in minimal receptor-binding domain with SARS-CoV. Addition of a novel glycosylation sites were observed in 2019-nCoV. In addition, antigenic analysis proposes that great antigenic differences exist between both the viral strains, but some of the epitopes were found to be similar between both the S proteins. In spite of the variation in S protein amino acid composition, we found no significant difference in their structures. Collectively, for the first time our results exhibit the emergence of human 2019-nCoV is closely related to predecessor SARS-CoV and provide the evidence that 2019-nCoV uses various novel glycosylation sites as SARS-CoV and may have a potential to become pandemic owing its antigenic discrepancy. Further, demonstration of novel Cytotoxic T lymphocyte epitopes may impart opportunities for the development of peptide based vaccine for the prevention of 2019-nCoV.

Current Insight into the Novel Coronavirus Disease 2019 (COVID-19)

“…So far, studies have not been conducted that reveal the peptide presentation. However, CTL epitopes of SARS-CoV-2 have been predicted by several studies, which may be used for understanding the pathogenesis and development of peptide-based vaccines (Kumar et al 2020;Walls et al 2020). Studies have been conducted in SARS-CoV-2 infected patients showing the activation and reduction in CD4 + and CD8 + T cell counts (Li et al 2020a).…”

“…S protein is responsible for the attachment and entry of SARS-CoV-2 to the host target cell receptor, probably angiotensin-converting enzyme 2 (ACE2) mainly expressed on alveolar epithelial type II (AECII) cells, including extrapulmonary tissues such as heart, kidney, endothelium, and intestine ). SARS-CoV-2 has been shown to exhibit novel glycosylation sites in the spike glycoprotein of 2019-nCoV, suggesting that the virus may utilize different glycosylation sites to interact with its receptors (Kumar et al 2020). Studies have demonstrated that SARS-CoV-2 spike protein has higher affinity to the ACE2 receptor as compared with SARS (Walls et al 2020).…”

Therapeutic Development and Drugs for the Treatment of COVID-19

“…The virus infection leads to 245,922 confirmed cases and 10,048 deaths worldwide as of March 20, 2020(ProMED-mail 2020. SARS-CoV-2 and SARS are clinically similar, and recent studies have shown that SARS-CoV-2 is closely related to SARS-CoV (Kumar et al 2020). The cause and spread of SARS-CoV-2 outbreak are still unclear.…”

Mass spectrometry analysis of newly emerging coronavirus HCoV-19 spike S protein and human ACE2 reveals camouflaging glycans and unique post-translational modifications

“…Additionally, C-type lectin DC-SIGN and L-SIGN can enhance viral entry via their binding to the S protein glycans (Han et al, 2007; Jeffers et al, 2004). Therefore, numerous antiviral strategies have been designed to interfere protein glycosylation or glycan-based interaction (Shih et al, 2006; Vincent et al, 2005; Zheng et al, 2020; Zhou et al, 2010), and glycosylation is considered as a key aspect to develop effective vaccine (Chen et al, 2014; Kumar et al, 2020).…”