SARS-CoV-2 and ORF3a: Non-Synonymous Mutations and Polyproline Regions

Issa, Elio; Merhi, Georgi; Panossian, Balig; Salloum, Tamara; Tokajian, Sima

doi:10.1101/2020.03.27.012013

Cited by 23 publications

(22 citation statements)

References 16 publications

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“…Other viral proteins showed mutations in multiple positions, although the mutation rates are notably lower ( Figure S1). Changes in residue Q57 in the NS3 (MR=0.11) [20] or residue L37 in the NSP6 (MR=0.06) should also be further monitored. More studies would be necessary to clarify their implication in the viral cycle life.…”

Section: Ns9c Accessory Proteinmentioning

confidence: 99%

One Year of SARS-CoV-2: How Much Has the Virus Changed?

Vilar¹,

Isom

2020

Preprint

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SARS-CoV-2 coronavirus has caused a world-wide crisis with profound effects on both healthcare and the economy. In order to combat the COVID-19 pandemic, research groups have shared viral genome sequence data through the GISAID initiative. We collected and computationally profiled ∼223,000 full SARS-CoV-2 proteome sequences from GISAID over one year for emergent nonsynonymous mutations. Our analysis shows that SARS-CoV-2 proteins are mutating at substantially different rates, with most viral proteins exhibiting little mutational variability. As anticipated, our calculations capture previously reported mutations occurred in the first period of the pandemic, such as D614G (Spike), P323L (NSP12), and R203K/G204R (Nucleocapsid), but also identify recent mutations like A222V and L18F (Spike) and A220V (Nucleocapsid). Our comprehensive temporal and geographical analyses show two periods with different mutations in the SARS-CoV-2 proteome: December 2019 to June 2020 and July to November 2020. Some mutation rates differ also by geography; the main mutations in the second period occurred in Europe. Furthermore, our structure-based molecular analysis provides an exhaustive assessment of mutations in the context of 3D protein structure. Emerging sequence-to-structure data is beginning to reveal the site-specific mutational tolerance of SARS-CoV2 proteins as the virus continues to spread around the globe.

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Section: Ns9c Accessory Proteinmentioning

confidence: 99%

One Year of SARS-CoV-2: How Much Has the Virus Changed?

Vilar¹,

Isom

2020

Preprint

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“…Based on its function in SARS-CoV, it has been postulated that Orf3a is involved in cell apoptosis. 7 Mutations in Orf3a in SARS-Cov-2 have been shown to also result in loss or change of epitopes that may help the virus evade the host immune response 7 . There may be clinical implications of the missense mutations of these proteins.…”

Section: The Potential Impact Of the Emergence Of Group D And E Sars-mentioning

confidence: 99%

Identification of novel missense mutations in a large number of recent SARS-CoV-2 genome sequences

Cai

2020

Preprint

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Background. SARS-CoV-2 infection has spread to over 200 countries since it was first reported in December of 2019. Significant country-specific variations in infection and mortality rate have been noted. Although country-specific differences in public health response have had a large impact on infection rate control, it is currently unclear as to whether evolution of the virus itself has also contributed to variations in infection and mortality rate. Previous studies on SARS-CoV-2 mutations were based on the analysis of ~ 160 SARS-CoV-2 sequences available until mid-February 2020. 2, 3, 4, 5 By mid-April, > 550 SARS-CoV-2 sequences had been deposited in GenBank, and over 8,200 in the GISAID database. Methods. We performed a sequence analysis on 474 SARS-CoV-2 genomes submitted to GenBank up to April 11, 2020 by multiple alignment using Map to a Reference Assembly and Variants/SNP identification. The results were verified on a larger scale, 8,126 hCoV-19 (SARS-CoV-2) sequences from GISAID database. Results. We identified 5 recently emerged mutations in many isolates (up to 40%). Our analysis highlights 5 frequent new mutations that have emerged since late February 2020. These mutations are: one each missense (non-synonymous) mutation in orf1ab (C1059T), orf3 (G25563T) and orf8 (C27964T), one in 5’UTR (C241T), one in a non-coding region (G29553A). The final mutation (G29553A) was found to be almost exclusive to the US isolates. The first 3 mutations are non-synonymous, leading to amino acid substitutions in the viral protein sequence. Except for C241T, all the novel mutations identified are absent in the isolates from Italy and Spain in the SARS-CoV-2 genomes deposited in GenBank and GISAID. Conclusion. The results of current study indicate that new mutations are emerging as COVID-19 pandemic are spreading to different countries and that geography specific mutants exist. The findings of current study lay the foundation for further investigation into the impact of SARS-CoV-2 mutations on disease incidence, severity, and host immune response. In addition, it may also provide insights into vaccine development and serological response detection for the virus.

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“…The D614G mutation has been reported to cause a decrease in PCR cycle thresholds, suggestive of higher upper respiratory tract viral load ( Grubaugh et al, 2020 ; Korber et al, 2020 ) in the host. A previously reported deleterious variation in the protein expressed from ORF3a, Q57H ( Issa et al, 2020 ; Laha et al, 2020 ), was recorded in Oklahoma-ADDL-1, the genome isolated at the beginning of the pandemic in Oklahoma. This mutation was not recorded in genomes isolated at other times in the state.…”

Section: Resultsmentioning

confidence: 95%

SARS-CoV-2 Genomes From Oklahoma, United States

et al. 2021

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Genomic sequencing has played a major role in understanding the pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the current pandemic, it is essential that SARS-CoV-2 viruses are sequenced regularly to determine mutations and genomic modifications in different geographical locations. In this study, we sequenced SARS-CoV-2 from five clinical samples obtained in Oklahoma, United States during different time points of pandemic presence in the state. One sample from the initial days of the pandemic in the state and four during the peak in Oklahoma were sequenced. Previously reported mutations including D614G in S gene, P4715L in ORF1ab, S194L, R203K, and G204R in N gene were identified in the genomes sequenced in this study. Possible novel mutations were also detected in the S gene (G1167V), ORF1ab (A6269S and P3371S), ORF7b (T28I), and ORF8 (G96R). Phylogenetic analysis of the genomes showed similarity to other SARS-CoV-2 viruses reported from across the globe. Structural characterization indicates that the mutations in S gene possibly influences conformational flexibility and motion of the spike protein, and the mutations in N gene are associated with disordered linker region within the nucleocapsid protein.

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SARS-CoV-2 and ORF3a: Non-Synonymous Mutations and Polyproline Regions

Cited by 23 publications

References 16 publications

One Year of SARS-CoV-2: How Much Has the Virus Changed?

One Year of SARS-CoV-2: How Much Has the Virus Changed?

Identification of novel missense mutations in a large number of recent SARS-CoV-2 genome sequences

SARS-CoV-2 Genomes From Oklahoma, United States

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