Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design

Kames, Jacob; Holcomb, David D.; Kimchi, Ofer; DiCuccio, Michael; Hamasaki-Katagiri, Nobuko; Wang, Tony; Komar, Anton A.; Alexaki, Aikaterini; Kimchi-Sarfaty, Chava

doi:10.1038/s41598-020-72533-2

Cited by 50 publications

(40 citation statements)

References 51 publications

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“…N protein was highly homogeneous to SARS-CoV (∼90%) and shared sequence similarity to other human CoVs (19-45%). However, S1 subunit of SARS-CoV-2 share only 64% and 57% with SARS-CoV and MERS-CoV, respectively, and 9-37% with other human CoVs( Kames et al, 2020 ). S2 subunit shows 88% sequence homology with the SARS-CoV( Huang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Clinical applications of detecting IgG, IgM or IgA antibody for the diagnosis of COVID-19: A meta-analysis and systematic review

Chen¹,

Qin²,

Jiang³

et al. 2021

International Journal of Infectious Diseases

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Section: Discussionmentioning

confidence: 99%

Clinical applications of detecting IgG, IgM or IgA antibody for the diagnosis of COVID-19: A meta-analysis and systematic review

Chen¹,

Qin²,

Jiang³

et al. 2021

International Journal of Infectious Diseases

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“…As already mentioned, amplicon-based and metagenomic approaches based on the sequence-independent single primer amplification (SISPA) method are able to detect mutations occurring in the sequence of SARS-CoV-2 and potentially associated with vaccine inefficacy or resistance to antiviral therapies ( 110 , 111 ). Examples of this type of sequencing technique are the MinION and IDbyDNA platforms produced by Oxford Nanopore Technologies and Illumina, respectively ( 112 ).…”

Section: Alternative Methods For the Effective Diagnosis Of Covid-mentioning

confidence: 99%

Current and innovative methods for the diagnosis of COVID‑19 infection (Review)

et al. 2021

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The Coronavirus Disease 2019 (COVID-19) pandemic has forced the scientific community to rapidly develop highly reliable diagnostic methods in order to effectively and accurately diagnose this pathology, thus limiting the spread of infection. Although the structural and molecular characteristics of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were initially unknown, various diagnostic strategies useful for making a correct diagnosis of COVID-19 have been rapidly developed by private research laboratories and biomedical companies. At present, rapid antigen or antibody tests, immunoenzymatic serological tests and molecular tests based on RT-PCR are the most widely used and validated techniques worldwide. Apart from these conventional methods, other techniques, including isothermal nucleic acid amplification techniques, clusters of regularly inter-spaced short palindromic repeats/Cas (CRISPR/Cas)-based approaches or digital PCR methods are currently used in research contexts or are awaiting approval for diagnostic use by competent authorities. In order to provide guidance for the correct use of COVID-19 diagnostic tests, the present review describes the diagnostic strategies available which may be used for the diagnosis of COVID-19 infection in both clinical and research settings. In particular, the technical and instrumental characteristics of the diagnostic methods used are described herein. In addition, updated and detailed information about the type of sample, the modality and the timing of use of specific tests are also discussed.

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“…The Orf7a protein has a known Ig-like structure and exhibits large genome-level variation and yet relative conservation as a single protein family, whereas Orf8, which is predicted to have a similar Ig-like structure, exhibits fewer genome-level variations apart from the split a/b pair or a full deletion and is quite variable at the protein sequence level. It should be noted that neither specific disordered regions have been detected for either of the two genes (36) nor any peculiar codon usage patterns (37). However, this peculiar trajectory of Orf8/Orf7a in SARS-CoV-2 indicates a stealth viral strategy that might be key to control virulence and pathogenicity, with roles in host cell-virus interactions.…”

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confidence: 89%

Atypical Divergence of SARS-CoV-2 Orf8 from Orf7a within the Coronavirus Lineage Suggests Potential Stealthy Viral Strategies in Immune Evasion

Neches

Kyrpides

Ouzounis

2021

mBio

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Orf8, one of the most puzzling genes in the SARS lineage of coronaviruses, marks a unique and striking difference in genome organization between SARS-CoV-2 and SARS-CoV-1. Here, using sequence comparisons, we unequivocally reveal the distant sequence similarities between SARS-CoV-2 Orf8 with its SARS-CoV-1 counterparts and the X4-like genes of coronaviruses, including its highly divergent “paralog” gene Orf7a, whose product is a potential immune antagonist of known structure. Supervised sequence space walks unravel identity levels that drop below 10% and yet exhibit subtle conservation patterns in this novel superfamily, characterized by an immunoglobulin-like beta sandwich topology. We document the high accuracy of the sequence space walk process in detail and characterize the subgroups of the superfamily in sequence space by systematic annotation of gene and taxon groups. While SARS-CoV-1 Orf7a and Orf8 genes are most similar to bat virus sequences, their SARS-CoV-2 counterparts are closer to pangolin virus homologs, reflecting the fine structure of conservation patterns within the SARS-CoV-2 genomes. The divergence between Orf7a and Orf8 is exceptionally idiosyncratic, since Orf7a is more constrained, whereas Orf8 is subject to rampant change, a peculiar feature that may be related to hitherto-unknown viral infection strategies. Despite their common origin, the Orf7a and Orf8 protein families exhibit different modes of evolutionary trajectories within the coronavirus lineage, which might be partly attributable to their complex interactions with the mammalian host cell, reflected by a multitude of functional associations of Orf8 in SARS-CoV-2 compared to a very small number of interactions discovered for Orf7a. IMPORTANCE Orf8 is one of the most puzzling genes in the SARS lineage of coronaviruses, including SARS-CoV-2. Using sophisticated sequence comparisons, we confirm its origins from Orf7a, another gene in the lineage that appears as more conserved, compared to Orf8. Orf7a is a potential immune antagonist of known structure, while a deletion of Orf8 was shown to decrease the severity of the infection in a cohort study. The subtle sequence similarities imply that Orf8 has the same immunoglobulin-like fold as Orf7a, confirmed by structure determination. We characterize the subgroups of this superfamily and demonstrate the highly idiosyncratic divergence patterns during the evolution of the virus.

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Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design

Cited by 50 publications

References 51 publications

Clinical applications of detecting IgG, IgM or IgA antibody for the diagnosis of COVID-19: A meta-analysis and systematic review

Clinical applications of detecting IgG, IgM or IgA antibody for the diagnosis of COVID-19: A meta-analysis and systematic review

Current and innovative methods for the diagnosis of COVID‑19 infection (Review)

Atypical Divergence of SARS-CoV-2 Orf8 from Orf7a within the Coronavirus Lineage Suggests Potential Stealthy Viral Strategies in Immune Evasion

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