SARS-CoV-2 SPIKE PROTEIN: an optimal immunological target for vaccines

Salvatori, Giovanni; Luberto, Laura; Maffei, Mariano; Aurisicchio, Luigi; Roscilli, Giuseppe; Palombo, Fabio; Marra, Emanuele

doi:10.1186/s12967-020-02392-y

Cited by 168 publications

(162 citation statements)

References 11 publications

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“…The envelope spike protein S, and the unexposed nucleocapsid protein N, are among the most promising targets for vaccine development against SARS-Cov-2 [44][45][46]. However, the detection of 1,966 point mutations (1,246 transitions with 402 C→U substitutions and 720 transversions with 239 G→U substitutions), distributed almost evenly across the total length of the S locus in the SARS-Cov-2 pan-genome ( Table 1, and Supplementary File 1, Table S1) 425 seriously questions the prospects of eventual effectiveness of S-targeting vaccines.…”

Section: Evolutionary/pathogenic Significance Of Copious Mutations Inmentioning

confidence: 99%

Trends of Mutation Accumulation Across Global SARS-CoV-2 Genomes: Implications for the Evolution of the Novel Coronavirus

Roy¹,

Mandal²,

Mondol³

et al. 2020

Preprint

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To understand SARS-CoV-2 microevolution, this study explored the genome-wide frequency, gene-wise distribution, and molecular nature of all point-mutations detected across its 71,703 RNA-genomes deposited in the GISAID repository, till 21 August 2020. Globally, nsp1/nsp2/nsp3/ nsp11 and orf7a/orf3a/S were the most mutation-ridden non-structural and structural genes respectively. Phylogeny based on 4,618 spatiotemporally-representative genomes revealed that entities belonging to the early lineages are mostly spread over Asian countries (including India, the biggest hotspot of the pandemic) whereas the recently-derived lineages are more globally distributed. Of the total 16,602 polymorphism-bearing sites in the pan-genome, 11,037 and 4,965 involved transitions and transversions, which in turn were predominated by cytidine-to-uridine and guanosine-to-uridine conversions, respectively. Positive selection of nonsynonymous mutations (dN/dS >1) in most of the structural, but not non-structural, genes indicated that SARS-CoV-2 has already harmonized its replication/transcription machineries with the host’s metabolic system, while it is still redefining virulence/transmissibility strategies at the molecular level.

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Section: Evolutionary/pathogenic Significance Of Copious Mutations Inmentioning

confidence: 99%

Trends of Mutation Accumulation Across Global SARS-CoV-2 Genomes: Implications for the Evolution of the Novel Coronavirus

Roy¹,

Mandal²,

Mondol³

et al. 2020

Preprint

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show abstract

“…However, some patients recover without producing high levels of nAbs and those with severe disease may experience an early rise in nAbs ( 30 ). Nevertheless, most vaccine efforts are focused on the induction of nAbs to the S protein in order to block attachment of RBD to the ACE2 receptor on host cells ( 31 ). As mentioned before, this domain is hidden in the S protein's prefusion state, presenting challenges to the success of RBD-based vaccines ( 16 ).…”

Section: Immune Response To Sars-cov-2mentioning

confidence: 99%

Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines

et al. 2020

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There are currently around 200 SARS-CoV-2 candidate vaccines in preclinical and clinical trials throughout the world. The various candidates employ a range of vaccine strategies including some novel approaches. Currently, the goal is to prove that they are safe and immunogenic in humans (phase 1/2 studies) with several now advancing into phase 2 and 3 trials to demonstrate efficacy and gather comprehensive data on safety. It is highly likely that many vaccines will be shown to stimulate antibody and T cell responses in healthy individuals and have an acceptable safety profile, but the key will be to confirm that they protect against COVID-19. There is much hope that SARS-CoV-2 vaccines will be rolled out to the entire world to contain the pandemic and avert its most damaging impacts. However, in all likelihood this will initially require a targeted approach toward key vulnerable groups. Collaborative efforts are underway to ensure manufacturing can occur at the unprecedented scale and speed required to immunize billions of people. Ensuring deployment also occurs equitably across the globe will be critical. Careful evaluation and ongoing surveillance for safety will be required to address theoretical concerns regarding immune enhancement seen in previous contexts. Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. We provide details of some of the frontrunner vaccines and discuss potential issues including adverse effects, scale-up and delivery.

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“…There are other analytical and biophysical tools which can provide detailed information on the binding affinity of the biomolecules, such as Förster resonance energy transfer (FRET) and biosensors (also FRET-based biosensors) [ 99 , 100 , 101 ], and isothermal titration calorimetry (ITC) [ 102 , 103 , 104 ], however, this is not in the scope of this review. The choice of the experimental strategy is usually dictated by the proteins under investigation.…”

Section: Spike Glycoproteinsmentioning

confidence: 99%

“…It is worth mentioning that, five years after the first SARS outbreak, a range of candidate vaccines have been developed. However, as of July 2020, there are no approved vaccines or drugs against any human-infecting CoV infections [ 48 , 53 , 104 ].…”

Section: Spike Glycoproteinsmentioning

confidence: 99%

Mass Spectrometry and Structural Biology Techniques in the Studies on the Coronavirus-Receptor Interaction

Witkowska

2020

Molecules

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Mass spectrometry and some other biophysical methods, have made substantial contributions to the studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human proteins interactions. The most interesting feature of SARS-CoV-2 seems to be the structure of its spike (S) protein and its interaction with the human cell receptor. Mass spectrometry of spike S protein revealed how the glycoforms are distributed across the S protein surface. X-ray crystallography and cryo-electron microscopy made huge impact on the studies on the S protein and ACE2 receptor protein interaction, by elucidating the three-dimensional structures of these proteins and their conformational changes. The findings of the most recent studies in the scope of SARS-CoV-2-Human protein-protein interactions are described here.

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SARS-CoV-2 SPIKE PROTEIN: an optimal immunological target for vaccines

Cited by 168 publications

References 11 publications

Trends of Mutation Accumulation Across Global SARS-CoV-2 Genomes: Implications for the Evolution of the Novel Coronavirus

Trends of Mutation Accumulation Across Global SARS-CoV-2 Genomes: Implications for the Evolution of the Novel Coronavirus

Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines

Mass Spectrometry and Structural Biology Techniques in the Studies on the Coronavirus-Receptor Interaction

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