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:10.1016/j.chom.2021.11.005

Cited by 163 publications

(152 citation statements)

References 80 publications

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“…In contrast, the neutralization titres for the R203M mutation group increased by 1.16- to 2.22-fold, with a mean of 1.49-fold (1/NT 50 : 0.45- to 0.86-fold, mean 0.67-fold) (Fig. 4A, B), which is consistent with our previous finding that the N protein 203 mutation confers increased susceptibility of SARS-CoV-2 to serum neutralization 23 . Interestingly, further reduced neutralization titres for the joint mutants L452R/R203M and L452R/R203K were found in the sera collected from hamsters, with 1.65- to 5.52-fold (mean 3.28-fold) and 1.71- to 5.07-fold (mean 3.07-fold) reductions when compared with those for the wild-type virus (Fig.…”

Section: Resultssupporting

confidence: 91%

“…Thereafter, we compared the growth rate between the 203K/484K/501Y variant and the R203/484K/501Y variant at different geographical levels. We did not consider D614G in this comparison because this mutation has been fixed in virus genomes around the world (Fig 1L) since July 2020 23,28 . In line with the results of the comparison results between the Gamma and Beta variants, the growth rate of the 203K/484K/501Y variant was consistently higher than that of the R203/484K/501Y variant (Figs.…”

Section: Resultsmentioning

confidence: 99%

“…This is essential for the development of vaccines and medicines. Our previous work reported the rapid spread of the R203K/G204R mutation 12 and further adaptiveness of the mutation 23 . In our consistent tracking of the mutations occurring in VOCs, we noticed that the newly evolved dominant lineage Delta possesses an R203M mutation in the N protein instead of the R203K/G204R mutations.…”

Section: Discussionmentioning

confidence: 96%

“…In addition to these adaptive S protein mutations, there are adaptive mutations in other parts of the viral genome that contribute to the virulence, spread and immune evasion of the virus. Several researchers have highlighted the potential importance of mutations in the nucleocapsid (N) protein 12,23-25 . Our previous work has found that the cooccurring mutations R203K/G204R in the N protein increase fitness and infectivity of SARS-CoV-2 and facilitate the emergence of the Alpha variant 23 .…”

Section: Introductionmentioning

confidence: 99%

“…Several researchers have highlighted the potential importance of mutations in the nucleocapsid (N) protein 12,23-25 . Our previous work has found that the cooccurring mutations R203K/G204R in the N protein increase fitness and infectivity of SARS-CoV-2 and facilitate the emergence of the Alpha variant 23 . The R203K/G204R mutations, dominant in the worldwide pandemic until May 2021, enhance the fitness of SARS-CoV-2 and are associated with the increased transmission and virulence of the Alpha variant.…”

Section: Introductionmentioning

confidence: 99%

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Nucleocapsid 203 mutations enhance SARS-CoV-2 immune evasion

Lin

Xue

Zhang

et al. 2021

Preprint

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Previous work indicated that the nucleocapsid 203 mutation increase the virulence and transmission of the SARS-CoV-2 Alpha variant. However, Delta later outcompeted Alpha and other lineages, promoting a new wave of infections. Delta also possesses a nucleocapsid 203 mutation, R203M. Large-scale epidemiological analyses suggest a synergistic effect of the 203 mutation and the spike L452R mutation, associated with Delta expansion. Viral competition experiments demonstrate the synergistic effect in fitness and infectivity. More importantly, we found that the combination of R203M and L452R brings in a 3.2-fold decrease in neutralizing titers to the neutralizing serum relative to L452R-only virus. R203M/L452R show an increased fitness after the initiation of global vaccination programmes, possibly associated with the enhanced immune evasion. Another rapidly emerging variant Omicron also bears the 203 mutation. Thus, we proposed that nucleocapsid mutations play an essential role for the rise and predominance of variants in concern.

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nucleocapsid 203 mutations enhance SARS-CoV-2 immune evasion

Lin

Xue

Zhang

et al. 2021

Preprint

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

Sharma

Rai

Gautam

et al. 2022

Journal of Medical Virology

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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.

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The outbreak of SARS‐CoV‐2 Omicron lineages, immune escape, and vaccine effectivity

Zhou

Zhi

Teng

2022

Journal of Medical Virology

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As of November 2021, several SARS‐CoV‐2 variants appeared and became dominant epidemic strains in many countries, including five variants of concern (VOCs) Alpha, Beta, Gamma, Delta, and Omicron defined by the World Health Organization during the COVID‐19 pandemic. As of August 2022, Omicron is classified into five main lineages, BA.1, BA.2, BA.3, BA.4, BA.5 and some sublineages (BA.1.1, BA.2.12.1, BA.2.11, BA.2.75, BA.4.6) ( https://www.gisaid.org/ ). Compared to the previous VOCs (Alpha, Beta, Gamma, and Delta), all the Omicron lineages have the most highly mutations in the spike protein, and with 50 mutations accumulated throughout the genome. Early data indicated that Omicron BA.2 sublineage had higher infectivity and more immune escape than the early wild‐type (WT) strain, the previous VOCs, and BA.1. Recently, global surveillance data suggest a higher transmissibility of BA.4/BA.5 than BA.1, BA.1.1 and BA.2, and BA.4/BA.5 is becoming dominant strain in many countries globally.

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Nucleocapsid mutations R203K/G204R increase the infectivity, fitness, and virulence of SARS-CoV-2

Abstract: Highlights d SARS-CoV-2 nucleocapsid mutations R203K/G204R associate with B.1.1.7 (Alpha) emergence d R203K/G204R variants possess a replication advantage over the preceding lineages d R203K/G204R variants show enhanced infectivity and disease severity in the hamster model

Cited by 163 publications

References 80 publications

Nucleocapsid 203 mutations enhance SARS-CoV-2 immune evasion

Nucleocapsid 203 mutations enhance SARS-CoV-2 immune evasion

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

The outbreak of SARS‐CoV‐2 Omicron lineages, immune escape, and vaccine effectivity

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