A non-coding A-to-T Kozak site change related to the transmissibility of Alpha, Delta and Omicron VOCs

Yang, Jianing; Zhang, Guoqing; Yu, Dalang; Cao, Ruifang; Wu, Xiaoxian; Ling, Yunchao; Pan, Yi-Hsuan; Yi, Chunyan; Sun, Xiaoyu; Sun, Bing; Zhao, Guoping; Li, Yixue; Li, Haipeng

doi:10.1101/2021.04.30.442029

Cited by 8 publications

(9 citation statements)

References 71 publications

(127 reference statements)

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“…One of the other top 10 mutations is 28271delA (34%), a non-coding deletion upstream of the Nucleocapsid gene that entered the country by B.1.1.7 lineage. This deletion interacts with other defining mutations of B.1.1.7, such as N501Y, P681H, and T716I (Yang et al 2021), and along with N:D3L (28280G>C,28281A>T,28282T>A), which is also frequently observed (30%) in our cohort, can cause the high viral transmissibility of B.1.1.7 lineage. The next top mutations; S235F, Q27*, and Y144del, are also among the defining B.1.1.7 mutations, and minor differences in their frequency can be explained by the variability in sequence qualities which can affect the subsequent mutation detection.…”

Section: Resultssupporting

confidence: 52%

Disease waves of SARS-CoV-2 in Iran closely mirror global pandemic trends

Fattahi

Mohseni

Beheshtian

et al. 2021

Preprint

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SARS-CoV-2 genome surveillance projects provide a good measure of transmission and monitor the circulating SARS-CoV-2 variants at regional and global scales. Iran is one of the most affected countries still involved with the virus circulating in at least five significant disease waves, as of September 2021. Complete genome sequencing of 50 viral isolates in an early phase of outbreak in Iran, shed light on the origins and circulating lineages at that time. As part of a genomic surveillance program, we provided an additional 319 complete genomes from October 2020 onwards. The current study is the report of complete SARS-CoV-2 genome sequences of Iran in the March 2020-May 2021 time interval. We aimed to characterize the genetic diversity of SARS-CoV-2 in Iran over one year. Overall, 35 different lineages and 8 clades were detected. Temporal dynamics of the prominent SARS-CoV-2 clades/lineages circulating in Iran is comparable to the global perspective and introduces the 19A clade (B.4) dominating the first disease wave, followed by 20A (B.1.36), 20B (B.1.1.413), 20I (B.1.1.7) clades, dominating second, third and fourth disease waves, respectively. We observed a mixture of circulating 20A (B.1.36), 20B (B.1.1.413), 20I (B.1.1.7) clades in winter 2021, paralleled in a diminishing manner for 20A/20B and a growing rise for 20I, eventually prompting the 4th outbreak peak. Furthermore, our study provides evidence on the entry of the Delta variant in April 2021, leading to the 5th disease wave in summer 2021. Three lineages are highlighted as hallmarks of SARS-CoV-2 outbreak in Iran; B4, dominating early periods of the epidemic, B.1.1.413 (specific B.1.1 lineage carrying a combination of [D138Y-S477N-D614G] spike mutations) in October 2020-February 2021, and the co-occurrence of [I100T-L699I] spike mutations in half of B.1.1.7 sequences mediating the fourth peak. Continuous monthly monitoring of SARS-CoV-2 genome mutations led to the detection of 1577 distinct nucleotide mutations, in which the top recurrent mutations were D614G, P323L, R203K/G204R, 3037C>T, and 241C>T; the renowned combination of mutations in G and GH clades. The most frequent spike mutation is D614G followed by 13 other frequent mutations based on the prominent circulating lineages; B.1.1.7 (H69_V70del, Y144del, N501Y, A570D, P681H, T716I, S982A, D1118H, I100T, and L699I), B.1.1.413 (D138Y, S477N) and B.1.36 (I210del). In brief, mutation surveillance in this study provided a real-time comprehensive picture of the SARS-CoV-2 mutation profile in Iran, which is beneficial for evaluating the magnitude of the epidemic and assessment of vaccine and therapeutic efficiency in this population.

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Section: Resultssupporting

confidence: 52%

Disease waves of SARS-CoV-2 in Iran closely mirror global pandemic trends

Fattahi

Mohseni

Beheshtian

et al. 2021

Preprint

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“…A hallmark of VoC Alpha is a higher transmissibility compared to preexisting virus variants, and recent studies indicate that it also poses a higher risk of hospitalization and ICU admission [2][3][4][5][6]. VoC Alpha is characterized by several genomic mutations, one of which is found within its N gene and seems to increase the expression of a subgenomic open reading frame (ORF) encoding a small accessory protein termed Orf9b [7,8]. Recent unpublished data suggest that a sub-genomic RNA (sgRNA) encoding for Orf9b is expressed up to 16-fold in samples of patients infected with VoC Alpha, hinting at an important role of Orf9b for the pathogenicity of this variant [9].…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of SARS-CoV-2 Orf9b Regulates Its Targeting to Two Binding Sites in TOM70 and Recruitment of Hsp90

Brandherm

Kobaš

Klöhn

et al. 2021

IJMS

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SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the causative agent of the COVID19 pandemic. The SARS-CoV-2 genome encodes for a small accessory protein termed Orf9b, which targets the mitochondrial outer membrane protein TOM70 in infected cells. TOM70 is involved in a signaling cascade that ultimately leads to the induction of type I interferons (IFN-I). This cascade depends on the recruitment of Hsp90-bound proteins to the N-terminal domain of TOM70. Binding of Orf9b to TOM70 decreases the expression of IFN-I; however, the underlying mechanism remains elusive. We show that the binding of Orf9b to TOM70 inhibits the recruitment of Hsp90 and chaperone-associated proteins. We characterized the binding site of Orf9b within the C-terminal domain of TOM70 and found that a serine in position 53 of Orf9b and a glutamate in position 477 of TOM70 are crucial for the association of both proteins. A phosphomimetic variant Orf9bS53E showed drastically reduced binding to TOM70 and did not inhibit Hsp90 recruitment, suggesting that Orf9b–TOM70 complex formation is regulated by phosphorylation. Eventually, we identified the N-terminal TPR domain of TOM70 as a second binding site for Orf9b, which indicates a so far unobserved contribution of chaperones in the mitochondrial targeting of the viral protein.

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“…To detect ongoing positive selection, allele frequency trajectory with an S-shaped curve was examined (Table S3, Figures S14 and S15). To reduce the impact of hitchhiking by neutral mutation, only non-synonymous mutations were analyzed, although non-coding mutations [ 22 ] can also be beneficial (see Supplemental Materials and Methods Section 16).…”

Section: Methodsmentioning

confidence: 99%

“…The CGB also predicted an increase in the frequency of S:p.P681R of the Delta VOC (Figure S16), suggesting that variants with the mutation may be advantageous. S:p.P681R is located on the spike S1/S2 cleavage site, and another mutation (S:p.P681H) on the same position has been found to be advantageous [ 28 ] and may interact with other mutations [ 22 ] in the Alpha VOC. Based on 1,002,739 samples, the CGB detected 13 putative advantageous mutations in the spike protein (Table S4).…”

Section: Mutation Analysismentioning

confidence: 99%

Coronavirus GenBrowser for monitoring the transmission and evolution of SARS-CoV-2

Yang

Tang

et al. 2022

Briefings in Bioinformatics

Self Cite

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Genomic epidemiology is important to study the COVID-19 pandemic, and more than two million severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequences were deposited into public databases. However, the exponential increase of sequences invokes unprecedented bioinformatic challenges. Here, we present the Coronavirus GenBrowser (CGB) based on a highly efficient analysis framework and a node-picking rendering strategy. In total, 1,002,739 high-quality genomic sequences with the transmission-related metadata were analyzed and visualized. The size of the core data file is only 12.20 MB, highly efficient for clean data sharing. Quick visualization modules and rich interactive operations are provided to explore the annotated SARS-CoV-2 evolutionary tree. CGB binary nomenclature is proposed to name each internal lineage. The pre-analyzed data can be filtered out according to the user-defined criteria to explore the transmission of SARS-CoV-2. Different evolutionary analyses can also be easily performed, such as the detection of accelerated evolution and ongoing positive selection. Moreover, the 75 genomic spots conserved in SARS-CoV-2 but non-conserved in other coronaviruses were identified, which may indicate the functional elements specifically important for SARS-CoV-2. The CGB was written in Java and JavaScript. It not only enables users who have no programming skills to analyze millions of genomic sequences, but also offers a panoramic vision of the transmission and evolution of SARS-CoV-2.

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A non-coding A-to-T Kozak site change related to the transmissibility of Alpha, Delta and Omicron VOCs

Cited by 8 publications

References 71 publications

Disease waves of SARS-CoV-2 in Iran closely mirror global pandemic trends

Disease waves of SARS-CoV-2 in Iran closely mirror global pandemic trends

Phosphorylation of SARS-CoV-2 Orf9b Regulates Its Targeting to Two Binding Sites in TOM70 and Recruitment of Hsp90

Coronavirus GenBrowser for monitoring the transmission and evolution of SARS-CoV-2

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