Nucleocapsid Mutations R203K/G204R Increase the Infectivity, Fitness and Virulence of SARS-CoV-2

Wu, Haibo; Xing, Na; Meng, Kaiwen; Fu, Binying; Xue, Weiwei; Dong, Pan; Tang, Wanyan; Yang, Xiao; Liu, Gexin; Luo, Haitao; Zhu, Wenzhuang; Lin, Xiaoyuan; Meng, Geng; Zhu, Zhenglin

doi:10.2139/ssrn.3896432

Cited by 12 publications

(11 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SARS‐CoV‐2 variants with the 203K/204R mutation have higher transmission and virulence. Mutations in the nucleocapsid protein and spike protein are vital for viral spread during the pandemic 34 …”

Section: Genetic Mutations In Omicronmentioning

confidence: 99%

Emerging evidence on Omicron (B.1.1.529) SARS‐CoV‐2 variant

Sharma

Rai

Gautam

et al. 2022

Journal of Medical Virology

View full text Add to dashboard Cite

COVID's Omicron variant has sparked a slew of concerns across the globe. This review aims to provide a brief overview of what we know about the Omicron variant right now. The new variant has been discovered in 149 countries across all six World Health Organization (WHO) regions since its discovery in South Africa on November 24, 2021 and became the dominant variant in the country in less than 3 weeks. The WHO has warned that the B.1.1.529 variant is spreading at an unprecedented rate, and has urged countries to prepare for the worst. Over the course of this time, researchers from Africa and around the world have uncovered a wealth of information about the virus's epidemiology and biological properties. Case numbers are increasing exponentially in hard‐hit areas such as South Africa, United Kingdom, and USA (overtaking the delta variant), implying that the variant is highly transmissible. Initial research has provided some insights into the efficacy of vaccines against the Omicron variant and whether it produces major illness, however, much remains unknown, and additional work is needed to investigate what the initial reports represent in real‐world situations.

show abstract

Section: Genetic Mutations In Omicronmentioning

confidence: 99%

Emerging evidence on Omicron (B.1.1.529) SARS‐CoV‐2 variant

Sharma

Rai

Gautam

et al. 2022

Journal of Medical Virology

View full text Add to dashboard Cite

show abstract

“…In total, 37 SARS-CoV-2 isolates had 5’-UTR-derived sequences in their N gene, in contrast to ∼336,000 isolates with either R203K or G204K as per NCBI Virus (mutations in SARS-CoV-2 SRA data); most were isolates of the variant of concern gamma GR/501Yv3 (P1) lineage (first detected in Brazil and Japan) from Brazil, Chile, and Peru, but also alpha (B.1.1.7; first detected in Great Britain) from USA and Canada (Supplemental legend to Figure 4). The R203K/G204R co-mutation has been associated with B.1.1.7 (alpha) lineage emergence, which along with variants with the co-mutation including the P1 (gamma) lineage (Franco-Muñoz et al 2020), possess a replication advantage over the preceding lineages and show increased nucleocapsid phosphorylation, infectivity, replication, virulence, fitness, and pathogenesis as documented in a hamster model, human cells, and COVID-19 patients including an analysis of association between COVID-19 severity and sample frequency of R203K/G204R co-mutations (Johnson et al 2021; Mourier et al 2022; Wu et al 2021).…”

Section: Resultsmentioning

confidence: 99%

Intragenomic rearrangements of SARS-CoV-2 and other β-coronaviruses

Patarca

Haseltine

2022

Preprint

View full text Add to dashboard Cite

The continuation of the SARS-CoV-2 pandemic depends on the generation of new viral variants. Documented variation includes point mutations, deletions, insertions, and recombination among closely or distantly related coronaviruses. Here, we describe yet another aspect of genome variation by β-coronaviruses, including SARS-CoV-2. Specifically, we report numerous genomic insertions of 5′-untranslated region sequences into coding regions of SARS-CoV-2 and other beta-coronaviruses. To our knowledge this is the first systematic description of such insertions. In many cases, these insertions change viral protein sequences and further foster genomic flexibility and viral adaptability through insertion of transcription regulatory sequences in novel positions within the genome. Among human Embecorivus β-coronaviruses, for instance, from one-third to one-half of surveyed sequences in publicly available databases contain 5′-UTR-derived inserted sequences. In limited instances, there is mounting evidence that these insertions alter the fundamental biological properties of mutant viruses. Intragenomic rearrangements add to our appreciation of how SARS-CoV-2 variants may arise.

show abstract

“…In India, when vaccination was low during June 2021, the two strains of Delta reached similar levels, both occupying almost 50% of the total genomes [35]. Recently, few studies have highlighted the role of Nucleocapsid mutations in promoting higher infectivity and virulence of SARS-CoV-2 [36]. It was not only the Spike variations alone which allowed Delta to out-compete other variants in the second wave, rather the role of other non-Spike mutations have been underexplored to date [37][38].…”

Section: Discussionmentioning

confidence: 99%

“…Maximally, the emerging mutations encompass the Spike glycoprotein, which could modify the binding efficiency to host Angiotensin-Converting Enzyme 2 (ACE2) receptors, alter transmissibility and neutralization efficiency to specific antibodies [11][12]. Nevertheless, mutations across Nucleocapsid and other non-structural proteins might also have a significant impact on viral immune escape strategies, leading to symptomatic or asymptomatic infection [13].…”

Section: Introductionmentioning

confidence: 99%

Evolution of Delta variant by non-Spike signature co-appearing mutations: trailblazer of COVID-19 disease outcome

Banerjee

Mazumder

Roy

et al. 2022

Preprint

View full text Add to dashboard Cite

The high transmissibility and infectivity of a SARS-CoV-2 variant is usually ascribed to the Spike mutations, while emerging non-spike mutations might be a serious threat to the current Spike-recombinant vaccines. In addition to mutations in structural Spike glycoprotein, rapid accumulation of mutations across non-structural genes is leading to continuous virus evolution, altering its pathogenicity. We performed whole genome sequencing of SARS-CoV-2 positive samples collected from different clinical groups from eastern India, during the second pandemic wave (April-May, 2021). In addition to the several common spike mutations in Delta variant, two mutually explicit signature constellations of non-spike co-appearing mutations were identified, driving symptomatic and asymptomatic infections. We attempted to correlate these unique signatures of non-Spike co-appearing mutations to COVID-19 disease outcome. Results revealed that the Delta strains harboring a unique constellation of 9 non-spike co-appearing mutations could be the wheeler and dealer of symptomatic infection, even post vaccination. The strains predominantly driving asymptomatic infection possessed 7 non-spike co-appearing mutations, which were mutually exclusive in contrast to the set of mutations causing symptomatic disease. Phylodynamic analysis depicted high probability of emergence of these unique sub-clusters within India, with subsequent spread worldwide. Interestingly, some mutations of this signature were selected in Omicron and IHU variants, which suggest that gradual accumulation of such co-existing mutations may lead to emergence of more “vaccine-evading variants” in future. Hence, unfaltering genome sequencing and tracking of non-Spike mutations might be significant in formulation of any future vaccines against emerging SARS-CoV-2 variants that might evade the current vaccine-induced immunity.

show abstract

Nucleocapsid Mutations R203K/G204R Increase the Infectivity, Fitness and Virulence of SARS-CoV-2

Cited by 12 publications

References 0 publications

Emerging evidence on Omicron (B.1.1.529) SARS‐CoV‐2 variant

Emerging evidence on Omicron (B.1.1.529) SARS‐CoV‐2 variant

Intragenomic rearrangements of SARS-CoV-2 and other β-coronaviruses

Evolution of Delta variant by non-Spike signature co-appearing mutations: trailblazer of COVID-19 disease outcome

Contact Info

Product

Resources

About