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Functional and Structural Characterization of SARS-Cov-2 Spike Protein: An In Silico Study.

ABSTRACT:

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the global outbreak of coronavirus disease 2019 (Covid-19), which has been considered as a pandemic by WHO. SARS-CoV-2 encodes four major structural proteins, among which spike protein has always been a main target for new vaccine studies. This in silico study aimed to investigate some physicochemical, functional, immunological, and structural features of spike protein using several bioinformatics tools.

Method

We retrieved all SARS-CoV-2 spike protein sequences from different countries registered in NCBI GenBank. CLC Sequence Viewer was employed to translate and align the sequences, and several programs were utilized to predict B-cell epitopes. Modification sites such as phosphorylation, glycosylation, and disulfide bonds were defined. Secondary and tertiary structures of all sequences were further computed.

Results

Some mutations were determined, where only one (D614G) had a high prevalence. The mutations did not impact the B-cell and physicochemical properties of the spike protein. Seven disulfide bonds were specified and also predicted in several N-link glycosylation and phosphorylation sites. The results also indicated that spike protein is a non-allergen.

Conclusion

In summary, our findings provided a deep understanding of spike protein, which can be valuable for future studies on SARS-CoV-2 infections and design of new vaccines.

SUBMITTER: Ebrahim-Saraie HS

PROVIDER: S-EPMC8188087 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:MOTIVATION:The recent emergence of the novel SARS-coronavirus 2 (SARS-CoV-2) and its international spread pose a global health emergency. The spike (S) glycoprotein binds ACE2 and promotes SARS-CoV-2 entry into host cells. The trimeric S protein binds the receptor using the receptor-binding domain (RBD) causing conformational changes in S protein that allow priming by host cell proteases. Unraveling the dynamic structural features used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal novel therapeutic targets. Using structures determined by X-ray crystallography and cryo-EM, we performed structural analysis and atomic comparisons of the different conformational states adopted by the SARS-CoV-2-RBD. RESULTS:Here, we determined the key structural components induced by the receptor and characterized their intramolecular interactions. We show that ?-helix (polyproline-II) is a predominant structure in the binding interface and in facilitating the conversion to the active form of the S protein. We demonstrate a series of conversions between switch-like ?-helix and ?-strand, and conformational variations in a set of short ?-helices which affect the hinge region. These conformational changes lead to an alternating pattern in conserved disulfide bond configurations positioned at the hinge, indicating a possible disulfide exchange, an important allosteric switch implicated in viral entry of various viruses, including HIV and murine coronavirus. The structural information presented herein enables to inspect and understand the important dynamic features of SARS-CoV-2-RBD and propose a novel potential therapeutic strategy to block viral entry. Overall, this study provides guidance for the design and optimization of structure-based intervention strategies that target SARS-CoV-2. AVAILABILITY:We have implemented the proposed methods in an R package freely available at https://github.com/Grantlab/bio3d. SUPPLEMENTARY INFORMATION:Supplementary data are available at Bioinformatics online.