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Natural heteroclitic-like peptides are generated by SARS-CoV-2 mutations.

ABSTRACT: Humoral immunity is sensitive to evasion by SARS-CoV-2 mutants, but CD8 T cells seem to be more resistant to mutational inactivation. By a systematic analysis of 30 spike variant peptides containing the most relevant VOC and VOI mutations that have accumulated overtime, we show that in vaccinated and convalescent subjects, mutated epitopes can have not only a neutral or inhibitory effect on CD8 T cell recognition but can also enhance or generate de novo CD8 T cell responses. The emergence of these mutated T cell function enhancing epitopes likely reflects an epiphenomenon of SARS-CoV-2 evolution driven by antibody evasion and increased virus transmissibility. In a subset of individuals with weak and narrowly focused CD8 T cell responses selection of these heteroclitic-like epitopes may bear clinical relevance by improving antiviral protection. The functional enhancing effect of these peptides is also worth of consideration for the future development of new generation, more potent COVID-19 vaccines.

SUBMITTER: Tiezzi C

PROVIDER: S-EPMC10200277 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Natural heteroclitic-like peptides are generated by SARS-CoV-2 mutations.

Tiezzi Camilla C Vecchi Andrea A Rossi Marzia M Cavazzini Davide D Bolchi Angelo A Laccabue Diletta D Doselli Sara S Penna Amalia A Sacchelli Luca L Brillo Federica F Meschi Tiziana T Ticinesi Andrea A Nouvenne Antonio A Donofrio Gaetano G Zanelli Paola P Benecchi Magda M Giuliodori Silvia S Fisicaro Paola P Montali Ilaria I Ceccatelli Berti Camilla C Reverberi Valentina V Montali Anna A Urbani Simona S Pedrazzi Giuseppe G Missale Gabriele G Telenti Amalio A Corti Davide D Ottonello Simone S Ferrari Carlo C Boni Carolina C

iScience 20230521 6

Humoral immunity is sensitive to evasion by SARS-CoV-2 mutants, but CD8 T cells seem to be more resistant to mutational inactivation. By a systematic analysis of 30 spike variant peptides containing the most relevant VOC and VOI mutations that have accumulated overtime, we show that in vaccinated and convalescent subjects, mutated epitopes can have not only a neutral or inhibitory effect on CD8 T cell recognition but can also enhance or generate <i>de novo</i> CD8 T cell responses. The emergence ...[more]

PMID: 37275517

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Project description:BackgroundA global pandemic owing to COVID-19 infection has created havoc in the entire world. The etiological agent responsible for this viral outbreak is classified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Still, there's no specific drug or preventive medication to treat SARS-CoV-2. This study was designed to demonstrate the efficacy of some anti-viral peptides obtained from a plant database i.e., PlantPepDB as potential ACE-2-Spike (S) protein complex neutralizers using a structure-based drug designing approach.MethodA total of 83 anti-viral plant peptides were screened from a peptide database i.e. PlantPepDB based on their reported anti-viral activities against various viral strains. In order to screen peptides that may potentially interfere with ACE-2 and S complex formation, molecular docking studies were conducted using the flare module of Cresset software and subsequently, analysed the crucial interactions between the peptides and S complexes and ACE-2/S complex. Herein, the interactions and docking scores obtained for ACE-2/S complex were considered as references. The S-peptides complexes which displayed superior interactions and docking scores than reference complex i.e., ACE2-S were considered as final hits. The Molecular dynamics studies were conducted for a period of 30 ns for each of the final hit/S complex to understand the interaction stability and binding mechanism of designed peptides.ResultsThe molecular docking results revealed that five peptides including Cycloviolacin Y3, Cycloviolacin Y1, White cloud bean defensin, Putative defensin 3.1, and Defensin D1 showed superior docking scores (i.e. -1372.5 kJ/mol to -1232.6 kJ/mol) when docked at the ACE2 binding site of S-protein than score obtained for the complex of ACE-2 and S protein i.e. -1183.4 kJ/mol. Moreover, these top five peptides manifested key interactions required to prevent the binding of S protein with ACE2. The molecular dynamics simulation study revealed that two of these five peptides i.e. Cycloviolacin Y3 and Cycloviolacin Y1 displayed minimal RMSD fluctuations.ConclusionsThe current structure-based drug-designing approach shows the possible role of anti-viral plant peptides as potential molecules to be explored at the initial stage of viral pathogenesis.

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Natural heteroclitic-like peptides are generated by SARS-CoV-2 mutations.

Publications

Natural heteroclitic-like peptides are generated by SARS-CoV-2 mutations.

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