Immunoinformatic analysis of structural and epitope variations in the spike and Orf8 proteins of SARS‐CoV‐2/B.1.1.7
| Autor: | Anusha Amanullah, Sanya Shabbir, Sahar Zahid, Muhammad J. Imdad, Mushtaq Hussain, Fozia Raza |
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| Rok vydání: | 2021 |
| Předmět: |
Lineage (genetic)
viruses Sequence alignment Genome Viral Biology spike protein SARS‐CoV‐2 Epitope Epitopes Viral Proteins 03 medical and health sciences 0302 clinical medicine COVID‐19 Virology Extracellular Humans Amino Acid Sequence 030212 general & internal medicine Homology modeling B.1.1.7 skin and connective tissue diseases Research Articles Immune Evasion SARS-CoV-2 Immunogenicity fungi COVID-19 Orf8 United Kingdom Stop codon respiratory tract diseases Cell biology body regions Infectious Diseases Spike Glycoprotein Coronavirus 030211 gastroenterology & hepatology Spike (software development) Immunotherapy Sequence Alignment Research Article |
| Zdroj: | Journal of Medical Virology |
| ISSN: | 1096-9071 0146-6615 |
| Popis: | A newly emerged strain of SARS‐CoV‐2 of B.1.1.7 lineage has caused a significant surge in the SARS‐CoV‐2 infections in the UK. In this study, changes in the epitopes of spike and orf8 proteins in SARS‐CoV‐2 of B.1.1.7 lineage were investigated. Genomic alignment of the SARS‐CoV‐2/B.1.1.7 with SARS‐CoV‐2/Wuhan showed the presence of several mutations in orf1a/b, spike, orf8, and N proteins of SARS‐CoV‐2/B.1.1.7. Molecular models of spike and orf8 proteins were constructed by homology modeling. Superimposition between the spike proteins of SARS‐CoV‐2/Wuhan and SARS‐CoV‐2/B.1.1.7 showed noticeable variations in the spatial orientation in Val70‐Asn74 and Thr250‐Ser255 regions. This may have also resulted in the extension of the epitopic region at Ser244‐Gly249 in the SARS‐CoV‐2/B.1.1.7 spike protein. Superimposition of the SARS‐CoV‐2/B.1.1.7 spike protein over Fab‐spike protein complexes of SARS‐CoV‐2/Wuhan also showed subtle variations in the antibody binding affinity targeting the N‐terminal domain of the spike protein. Epitopic variations were also observed between the corresponding orf8 regions of SARS‐CoV‐2/Wuhan and SARS‐CoV‐2/B.1.1.7. Moreover, the presence of a stop codon at position 27 in orf8 connotes the emergence of two frames (orf8a and orf8b) in SARS‐CoV‐2, which further hampers its extracellular secretion, and in turn, immunogenicity. The findings of the present study could further be used to develop targeted immunotherapeutics. |
| Databáze: | OpenAIRE |
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