Dataset Information

Selective pressure on SARS-CoV-2 protein coding genes and glycosylation site prediction.

ABSTRACT:

Background

An outbreak of a febrile respiratory illness due to the newly discovered Coronavirus, SARS-CoV-2, was initially detected in mid-December 2019 in the city of Wuhan, Hubei province (China). The virus then spread to most countries in the world. As an RNA virus, SARS-CoV-2 may acquire mutations that may be fixed. The aim of this study was to evaluate the selective pressure acting on SARS-CoV-2 protein coding genes.

Methods

Mutations and glycosylation site prediction were analyzed in SARS-CoV-2 genomes (from 464 to 477 sequences).

Results

Selective pressure on surface glycoprotein (S) revealed one positively selected site (AA 943), located outside the receptor binding domain (RBD). Mutation analysis identified five residues on the surface glycoprotein, with variations (AA positions 367, 458, 477, 483, 491) located inside the RDB. Positive selective pressure was identified in nsp2, nsp3, nsp4, nsp6, nsp12, helicase, ORF3a, ORF8, and N sub-sets. A total of 22 predicted N-glycosylation positions were found in the SARS-CoV-2 surface glycoprotein; one of them, 343N, was located within the RBD. One predicted N-glycosylation site was found in the M protein and 4 potential O-glycosylation sites in specific protein 3a sequences.

Conclusion

Overall, the data showed positive pressure and mutations acting on specific protein coding genes. These findings may provide useful information on: i) markers for vaccine design, ii) new therapeutic approach, iii) information to implement mutagenesis experiments to inhibit SARS-CoV-2 cell entry. The negative selection identified in SARS-CoV-2 protein coding genes may help the identification of highly conserved regions useful to implement new future diagnostic protocols.

SUBMITTER: Lo Presti A

PROVIDER: S-EPMC7505600 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

Selective pressure on SARS-CoV-2 protein coding genes and glycosylation site prediction.

Lo Presti Alessandra A Rezza Giovanni G Stefanelli Paola P

Heliyon 20200921 9

<h4>Background</h4>An outbreak of a febrile respiratory illness due to the newly discovered Coronavirus, SARS-CoV-2, was initially detected in mid-December 2019 in the city of Wuhan, Hubei province (China). The virus then spread to most countries in the world. As an RNA virus, SARS-CoV-2 may acquire mutations that may be fixed. The aim of this study was to evaluate the selective pressure acting on SARS-CoV-2 protein coding genes.<h4>Methods</h4>Mutations and glycosylation site prediction were an ...[more]

PMID: 32984566

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Project description:The SARS-CoV-2 spike protein is heavily glycosylated, having 22 predicted N-glycosylation sites per monomer. It is also O-glycosylated, although the number of O-glycosites is less defined. Recent studies show that spike protein glycans play critical roles in viral entry and infection. The spike monomer has two subdomains, S1 and S2, and a receptor-binding domain (RBD) within the S1 domain. In this study, we have characterized the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells. The Vero cell-derived spike from the WA1 strain and a D614G variant was analyzed. All spike proteins, S1, and RBDs were analyzed using hydrophilic interaction chromatography (HILIC) and LC-MS/MS on an Orbitrap Eclipse Tribrid mass spectrometer. N-glycans identified in HEK293-derived S1 were structurally diverse. Those found in the HEK293-derived RBD were highly similar to those in HEK293 S1 where N-glycosites were shared. Comparison of the whole cell-derived WA1 and D614G spike proteins revealed that N-glycosites local to the mutation site appeared to be more readily detected, hinting that these sites are more exposed to glycosylation machinery. Moreover, recombinant HEK293-derived S1 was occupied almost completely with complex glycan, while both WA1 and D614G derived from the Vero E6 cell whole virus were predominantly high-mannose glycans. This stands in stark contrast to glycosylation patterns seen in both CHO- and HEK cell-derived recombinant S1, S2, and the whole spike previously reported. Concerning O-glycosylation, our analyses revealed that HEK293 recombinant proteins possessed a range of O-glycosites with compositions consistent with Core type 1 and 2 glycans. The O-glycosites shared between the S1 and RBD constructs, sites T323 and T523, were occupied by a similar range of Core 1 and 2 type O-glycans. Overall, this study reveals that the sample nature and cell substrate used for production of these proteins can have a dramatic impact on the glycosylation profile. SARS-CoV-2 spike glycans are associated with host ACE2 receptor interaction efficiency. Therefore, understanding such differences will serve to better understand these host-pathogen interactions and inform the choice of cell substrates to suite downstream investigations.

Dataset Information

Selective pressure on SARS-CoV-2 protein coding genes and glycosylation site prediction.

Background

Methods

Results

Conclusion

Publications

Selective pressure on SARS-CoV-2 protein coding genes and glycosylation site prediction.

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