A SARS-CoV-2 vaccine candidate would likely match all currently circulating strains

Dearlove, Bethany L.; Lewitus, Éric; Bai, Hongjun; Li, Yifan; Reeves, Daniel B.; Joyce, Michael; Scott, Paul T.; Amare, Mihret F.; Vasan, Sandhya; Michael, Nelson L.; Modjarrad, Kayvon; Rolland, Morgane

doi:10.1101/2020.04.27.064774

Cited by 20 publications

(22 citation statements)

References 33 publications

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“…The vast majority of mutations observed so far in SARS-CoV-2 circulating in humans are likely neutral (Cagliani et al, 2020;Dearlove et al, 2020) or even deleterious (Nielsen et al, 2020). Homoplasies, such as those we detect here, can arise by product of neutral evolution or as a result of ongoing selection.…”

Section: Discussionmentioning

confidence: 99%

Emergence of genomic diversity and recurrent mutations in SARS-CoV-2

Dorp

Acman

Richard

et al. 2020

Infection, Genetics and Evolution

806

820

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SARS-CoV-2 is a SARS-like coronavirus of likely zoonotic origin first identified in December 2019 in Wuhan, the capital of China's Hubei province. The virus has since spread globally, resulting in the currently ongoing COVID-19 pandemic. The first whole genome sequence was published on January 5 2020, and thousands of genomes have been sequenced since this date. This resource allows unprecedented insights into the past demography of SARS-CoV-2 but also monitoring of how the virus is adapting to its novel human host, providing information to direct drug and vaccine design. We curated a dataset of 7666 public genome assemblies and analysed the emergence of genomic diversity over time. Our results are in line with previous estimates and point to all sequences sharing a common ancestor towards the end of 2019, supporting this as the period when SARS-CoV-2 jumped into its human host. Due to extensive transmission, the genetic diversity of the virus in several countries recapitulates a large fraction of its worldwide genetic diversity. We identify regions of the SARS-CoV-2 genome that have remained largely invariant to date, and others that have already accumulated diversity. By focusing on mutations which have emerged independently multiple times (homoplasies), we identify 198 filtered recurrent mutations in the SARS-CoV-2 genome. Nearly 80% of the recurrent mutations produced non-synonymous changes at the protein level, suggesting possible ongoing adaptation of SARS-CoV-2. Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. We additionally provide an interactive user-friendly web-application to query the alignment of the 7666 SARS-CoV-2 genomes.

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Section: Discussionmentioning

confidence: 99%

Emergence of genomic diversity and recurrent mutations in SARS-CoV-2

Dorp

Acman

Richard

et al. 2020

Infection, Genetics and Evolution

806

820

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“…Some suggested epitopes remain exposed regardless of the type or conformation of glycan chains at N-glycosylation sites on the SARS-CoV-2 trimeric spike. The S-protein of the SARS-CoV-2 has proven to be highly conserved this far into the pandemic 36 , supporting the selection of epitopes on the S-protein. As monoclonal antibodies enter clinical trials, it is crucial to monitor the sequence variation in the S-protein for potential escape mutants.…”

Section: (Supplementarymentioning

confidence: 91%

Impact of glycan cloud on the B-cell epitope prediction of SARS-CoV-2 Spike protein

Wintjens

Bifani

2020

npj Vaccines

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The SARS-CoV-2 outbreak originated in China in late 2019 and has since spread to pandemic proportions. Diagnostics, therapeutics and vaccines are urgently needed. We model the trimeric Spike protein, including flexible loops and all N-glycosylation sites, in order to elucidate accessible epitopes for antibody-based diagnostics, therapeutics and vaccine development. Based on published experimental data, six homogeneous glycosylation patterns and two heterogeneous ones were used for the analysis. The glycan chains alter the accessible surface areas on the S-protein, impeding antibody-antigen recognition. In presence of glycan, epitopes on the S1 subunit, that notably contains the receptor binding domain, remain mostly accessible to antibodies while those present on the S2 subunit are predominantly inaccessible. We identify 28 B-cell epitopes in the Spike structure and group them as nonaffected by the glycan cloud versus those which are strongly masked by the glycan cloud, resulting in a list of favourable epitopes as targets for vaccine development, antibody-based therapy and diagnostics.

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“…Such independence is the key to avoiding circularity in the subsequent analysis of the origin and spread of new mutants. For example, some early genome samples in China have been used as references in databases and analyses to orient mutational changes [15][16][17][18] . This practice assumes that reference genomes are ancestral.…”

Section: A Mutational History Of Sars-cov-2mentioning

confidence: 99%

An evolutionary portrait of the progenitor SARS-CoV-2 and its dominant offshoots in COVID-19 pandemic

Kumar

Tao

Weaver

et al. 2020

Preprint

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Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, was quickly identified as the cause of COVID-19 disease soon after its earliest reports. The knowledge of the contemporary evolution of SARS-CoV-2 is urgently needed not only for a retrospective on how, when, and why COVID-19 has emerged and spread, but also for creating remedies through efforts of science, technology, medicine, and public policy. Global sequencing of thousands of genomes has revealed many common genetic variants, which are the key to unraveling the early evolutionary history of SARS-CoV-2 and tracking its global spread over time. However, our knowledge of fundamental events in the evolution and spread of this coronavirus remains grossly incomplete and highly uncertain. Here, we present the heretofore cryptic mutational history, phylogeny, and dynamics of SARS-CoV-2 from an analysis of tens of thousands of high-quality genomes. The reconstructed mutational progression is highly concordant with the timing of coronavirus sampling dates. It predicts the progenitor genome whose earliest offspring without any non-synonymous mutations were still spreading worldwide months after the report of COVID-19. Over time, mutations gave rise to seven major lineages that spread episodically, some of which arose in Europe and North America after the genesis of the ancestral lineages in China. Mutational barcoding establishes that North American coronaviruses harbor very different genome signatures than coronaviruses prevalent in Europe and Asia that have converged over time. These spatiotemporal patterns continue to evolve as the pandemic progresses and can be viewed live online.

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A SARS-CoV-2 vaccine candidate would likely match all currently circulating strains

Cited by 20 publications

References 33 publications

Emergence of genomic diversity and recurrent mutations in SARS-CoV-2

Emergence of genomic diversity and recurrent mutations in SARS-CoV-2

Impact of glycan cloud on the B-cell epitope prediction of SARS-CoV-2 Spike protein

An evolutionary portrait of the progenitor SARS-CoV-2 and its dominant offshoots in COVID-19 pandemic

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