New variants of SARS-CoV-2

Cantón, Rafael; Ramos, Pilar; García‐Botella, Alejandra; García‐Lledó, Alberto; Gómez-Pavón, Javier; Castillo, Juan González del; Hernández-Sampelayo, Teresa; Martín-Delgado, M C; Sánchez, Francisco Javier Martín; Martínez‐Sellés, Manuel; García, José María Molero; Guillén, Santiago Moreno; Rodríguez‐Artalejo, Fernando; Ruiz-Galiana, Julián; Bouza, Emilio

doi:10.37201/req/071.2021

Cited by 58 publications

(60 citation statements)

References 25 publications

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“…The two lineages spread rapidly after they emerged 9 . 501Y Variant 2 was also named B.1.1.7 by COVID-19 Genomics Consortium UK (CoG-UK) 35 . It should be pointed out that the S protein of B.1.1.7 also had other mutations including P681H and Y144 deletion in addition to the penta-site mutation.…”

Section: No Holistic Change In the Antigenicity Of S Protein And Their Mutantsmentioning

confidence: 99%

Molecular dynamics simulation study reveals effects of key mutations on spike protein structure in SARS-CoV-2

Lon

Xi²,

Zhong³

et al. 2021

Preprint

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SARS-CoV-2 has been spreading rapidly since 2019 and has produced large-scale mutations in the genomes. Differences in gene sequences may lead to changes in protein structure and traits, which would have a great impact on the epidemiological characteristics. In this study, we selected the key mutations of SARS-CoV-2, including D614G and A222V of S protein and Q57H of ORF3a protein, to conduct molecular dynamics simulation and analysis on the structures of the mutant proteins. The results suggested that D614G improved the stability of S protein, while A222V enhanced the ability of protein to react with the outside environment. Q57H enhanced the structural flexibility of ORF3a protein. Our findings could complete the mechanistic link between genotype--phenotype--epidemiological characteristics in the study of SARS-CoV-2. We also found no significant changes in the antigenicity of S protein, ORF3a protein and their mutants, which provides reference for vaccine development and application.

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Section: No Holistic Change In the Antigenicity Of S Protein And Their Mutantsmentioning

confidence: 99%

Molecular dynamics simulation study reveals effects of key mutations on spike protein structure in SARS-CoV-2

Lon

Xi²,

Zhong³

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…This can be argued that the small sample size, restriction on the length of the construct, and manual shuffling of epitopes could be the reasons for such small changes. The next challenges are to work with a bigger dataset of variants, optimize the parameters influencing the MEBP vaccine design and gain deeper insights into the mechanisms behind the mutations and their virulence and improvise the MVP score incorporating the knowledge and the decision making systems such as AI and ML [62].…”

Section: Discussionmentioning

confidence: 99%

Epitope order Matters in multi-epitope-based peptide (MEBP) vaccine design: Anin silicostudy

Salaikumaran¹,

Kasamuthu²,

Burra³

2021

Preprint

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With different countries facing multiple waves, with some SARS-CoV-2 variants more deadly and virulent, the COVID-19 pandemic is becoming more dangerous by the day and the world is facing an even more dreadful extended pandemic with exponential positive cases and increasing death rates. There is an urgent need for more efficient and faster methods of vaccine development against SARS-CoV-2. Compared to experimental protocols, the opportunities to innovate are very high in immunoinformatics/in silico approaches especially with the recent adoption of structural bioinformatics in peptide vaccine design. In recent times, multi-epitope-based peptide vaccine candidates (MEBPVCs) have shown extraordinarily high humoral and cellular responses to immunization. Most of the publications claim that respective reported MEBPVC(s) assembled using a set of in silico predicted epitopes, to be the computationally validated potent vaccine candidate(s) ready for experimental validation. However, in this article, for a given set of predicted epitopes, it is shown that the published MEBPVC is one among the many possible variants and there is high likelihood of finding more potent MEBPVCs than the published candidate. To test the same, a methodology is developed where novel MEBP variants are derived by changing the epitope order of the published MEBPVC. Further, to overcome the limitations of current qualitative methods of assessment of MEBPVC, to enable quantitative comparison, ranking, and the discovery of more potent MEBPVCs, novel predictors, Percent Epitope Accessibility (PEA), Receptor specific MEBP vaccine potency(RMVP), MEBP vaccine potency(MVP) are introduced. The MEBP variants indeed showed varied MVP scores indicating varied immunogenicity. When the MEBP variants were ranked in descending order of their MVP scores, the published MEBPVC had the least MVP score. Further, the MEBP variants with IDs, SPVC_387 and SPVC_206, had the highest MVP scores indicating these variants to be more potent MEBPVCs than the published MEBPVC and hence should be prioritized for experimental testing and validation. Through this method, more vaccine candidates will be available for experimental validation and testing. This study also opens the opportunity to develop new software tools for designing more potent MEBPVCs in less time. The computationally validated top-ranked MEBPVCs must be experimentally tested, validated, and verified. The differences and deviations between experimental results and computational predictions provide an opportunity for improving and developing more efficient algorithms and reliable scoring schemes and software.

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“…Recently, the appearance and spread of new SARS-CoV-2 variants have produced enormous concern due to their possible implication in the improved transmissibility of the virus, their consequences in the individual evolution of the infection, as well as in the possible escape from the immunity generated by the current vaccines [130]. The variants that attracted most attention are those of public health concern, including B.1.1.7 (UK, Alpha), B.1.351 (South African, Beta) and P.1 (Brazilian, Gamma).…”

Section: Questions Addressing the Vaccination Against Sars-covmentioning

confidence: 99%

“…The variants that attracted most attention are those of public health concern, including B.1.1.7 (UK, Alpha), B.1.351 (South African, Beta) and P.1 (Brazilian, Gamma). This list is extended by the variants of interest that emerged and are expanding in certain countries but are solely found sporadically in others, such as B.1.427 and B.1.429 (Californians) or B.1.617 (Indian, Delta) [130] and C.37 (Lambda) [131]. Whole genome sequencing or strategies specifically targeting the spike gene are used for characterization and detection.…”

Section: Questions Addressing the Vaccination Against Sars-covmentioning

confidence: 99%

“…Whole genome sequencing or strategies specifically targeting the spike gene are used for characterization and detection. So far, it is not excluded that revaccination against new variants may be necessary in the future [130]. To date, a low or insignificant impact on vaccine efficacy against Alpha and Delta variants has been reported [131].…”

Section: Questions Addressing the Vaccination Against Sars-covmentioning

confidence: 99%

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Immune Responses against SARS-CoV-2—Questions and Experiences

et al. 2021

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Understanding immune reactivity against SARS-CoV-2 is essential for coping with the COVID-19 pandemic. Herein, we discuss experiences and open questions about the complex immune responses to SARS-CoV-2. Some people react excellently without experiencing any clinical symptoms, they do not get sick, and they do not pass the virus on to anyone else (“sterilizing” immunity). Others produce antibodies and do not get COVID-19 but transmit the virus to others (“protective” immunity). Some people get sick but recover. A varying percentage develops respiratory failure, systemic symptoms, clotting disorders, cytokine storms, or multi-organ failure; they subsequently decease. Some develop long COVID, a new pathologic entity similar to fatigue syndrome or autoimmunity. In reality, COVID-19 is considered more of a systemic immune–vascular disease than a pulmonic disease, involving many tissues and the central nervous system. To fully comprehend the complex clinical manifestations, a profound understanding of the immune responses to SARS-CoV-2 is a good way to improve clinical management of COVID-19. Although neutralizing antibodies are an established approach to recognize an immune status, cellular immunity plays at least an equivalent or an even more important role. However, reliable methods to estimate the SARS-CoV-2-specific T cell capacity are not available for clinical routines. This deficit is important because an unknown percentage of people may exist with good memory T cell responsibility but a low number of or completely lacking peripheral antibodies against SARS-CoV-2. Apart from natural immune responses, vaccination against SARS-CoV-2 turned out to be very effective and much safer than naturally acquired immunity. Nevertheless, besides unwanted side effects of the currently available vector and mRNA preparations, concerns remain whether these vaccines will be strong enough to defeat the pandemic. Altogether, herein we discuss important questions, and try to give answers based on the current knowledge and preliminary data from our laboratories.

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New variants of SARS-CoV-2

Cited by 58 publications

References 25 publications

Molecular dynamics simulation study reveals effects of key mutations on spike protein structure in SARS-CoV-2

Molecular dynamics simulation study reveals effects of key mutations on spike protein structure in SARS-CoV-2

Epitope order Matters in multi-epitope-based peptide (MEBP) vaccine design: Anin silicostudy

Immune Responses against SARS-CoV-2—Questions and Experiences

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