Objectives: Despite extensive efforts to monitor the diffusion of COVID-19, the actual wave of infection is worldwide characterized by the presence of emerging SARS-CoV-2 variants. The present study aims to describe the presence of yet undiscovered SARS-CoV-2 variants in Italy. Methods: Next Generation Sequencing was performed on 16 respiratory samples from occasionally employed within the Bangladeshi community present in Ostia and Fiumicino towns. Computational strategy was used to identify all potential epitopes for reference and mutated Spike proteins. A simulation of proteasome activity and the identification of possible cleavage sites along the protein guided to a combined score involving binding affinity, peptide stability and T-cell propensity. Results: Retrospective sequencing analysis revealed a double Spike D614G/S939F mutation in COVID-19 positive subjects present in Ostia while D614G mutation was evidenced in those based in Fiumicino. Unlike D614G, S939F mutation affects immune response by the slight but significant modulation of T-cell propensity and the selective enrichment of potential binding epitopes for some HLA alleles. Conclusion: Collectively, our findings mirror further the importance of deep sequencing of SARS-CoV-2 genome as a unique approach to monitor the appearance of specific mutations as for those herein reported for Spike protein. This might have implications on both the type of immune response triggered by the viral infection and the severity of the related illness.

Evidence of a SARS-CoV-2 double Spike mutation D614G/S939F potentially affecting immune response of infected subjects / Donzelli, S.; Spinella, F.; di Domenico, E. G.; Pontone, M.; Cavallo, I.; Orlandi, G.; Iannazzo, S.; Ricciuto, G. M.; ISG Virology Covid, Team; Pellini, R.; Muti, P.; Strano, S.; Ciliberto, G.; Ensoli, F.; Zapperi, S.; La Porta, C. A. M.; Blandino, G.; Morrone, A.; Pimpinelli, F.. - In: COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL. - ISSN 2001-0370. - 20:(2022), pp. 733-744. [10.1016/j.csbj.2022.01.021]

Evidence of a SARS-CoV-2 double Spike mutation D614G/S939F potentially affecting immune response of infected subjects

Donzelli S.;di Domenico E. G.;Pontone M.;Ricciuto G. M.;Ensoli F.;Zapperi S.;Blandino G.;Pimpinelli F.
2022

Abstract

Objectives: Despite extensive efforts to monitor the diffusion of COVID-19, the actual wave of infection is worldwide characterized by the presence of emerging SARS-CoV-2 variants. The present study aims to describe the presence of yet undiscovered SARS-CoV-2 variants in Italy. Methods: Next Generation Sequencing was performed on 16 respiratory samples from occasionally employed within the Bangladeshi community present in Ostia and Fiumicino towns. Computational strategy was used to identify all potential epitopes for reference and mutated Spike proteins. A simulation of proteasome activity and the identification of possible cleavage sites along the protein guided to a combined score involving binding affinity, peptide stability and T-cell propensity. Results: Retrospective sequencing analysis revealed a double Spike D614G/S939F mutation in COVID-19 positive subjects present in Ostia while D614G mutation was evidenced in those based in Fiumicino. Unlike D614G, S939F mutation affects immune response by the slight but significant modulation of T-cell propensity and the selective enrichment of potential binding epitopes for some HLA alleles. Conclusion: Collectively, our findings mirror further the importance of deep sequencing of SARS-CoV-2 genome as a unique approach to monitor the appearance of specific mutations as for those herein reported for Spike protein. This might have implications on both the type of immune response triggered by the viral infection and the severity of the related illness.
2022
D614G; Immune response; S939F; SARS-CoV-2; Spike mutations
01 Pubblicazione su rivista::01a Articolo in rivista
Evidence of a SARS-CoV-2 double Spike mutation D614G/S939F potentially affecting immune response of infected subjects / Donzelli, S.; Spinella, F.; di Domenico, E. G.; Pontone, M.; Cavallo, I.; Orlandi, G.; Iannazzo, S.; Ricciuto, G. M.; ISG Virology Covid, Team; Pellini, R.; Muti, P.; Strano, S.; Ciliberto, G.; Ensoli, F.; Zapperi, S.; La Porta, C. A. M.; Blandino, G.; Morrone, A.; Pimpinelli, F.. - In: COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL. - ISSN 2001-0370. - 20:(2022), pp. 733-744. [10.1016/j.csbj.2022.01.021]
File allegati a questo prodotto
File Dimensione Formato  
Donzelli_Evidence_2022.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 3.4 MB
Formato Adobe PDF
3.4 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1630479
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 4
social impact