SARS-CoV-2 spike E484K mutation reduces antibody neutralisation

Jangra, Sonia; Ye, Chengjin; Rathnasinghe, Raveen; Stadlbauer, Daniel; Krammer, Florian; Simon, Viviana; Martínez-Sobrido, Luis; Garcı́a-Sastre, Adolfo; Schotsaert, Michael

doi:10.1016/s2666-5247(21)00068-9

Cited by 380 publications

(343 citation statements)

References 4 publications

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“…Mutation E484K on S protein is present in different variants, such as B.1.351 (South Africa) and B.1.1.28 (Brazil), which has been interesting for being in the receptor-binding domain of spike protein and its relationship with the evasion of the immune response [9]. Intriguingly, despite having appeared in the same month of the second group of the HF mutations (those that characterize lineage B.1.1.7), this mutation corresponds to the MF type of dynamic (Fig.…”

Section: Discussionmentioning

confidence: 99%

Dynamics of SARS-CoV-2 mutations reveals regional-specificity and similar trends of N501 and High-Frequency mutation N501Y in different levels of control measures

et al. 2021

Preprint

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Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This disease has spread globally, causing more than 161.5 million cases and 3.3 million deaths. Keeping on the identification, surveillance and the study of the temporal dynamics of mutations with significant representation is central to understand the adaptation of SARS-CoV-2. Furthermore, how lockdown policies influence the dynamics of SARS-CoV-2 mutations is poorly understood. Here, using 1 058 020 SARS-CoV-2 genomes and COVID-19 cases from 714 country-month combinations representing 98 countries, we performed a normalization by COVID-19 cases calculation of relative frequency of SARS-CoV-2 mutations. We found 115 mutations estimated to be present in more than 3 % of global COVID-19 cases and determined three types of mutation dynamics: High-Frequency, Medium-Frequency, and Low-Frequency. Classification of mutations based on temporal dynamics helps to study viral adaptation and can be used to evaluate the effects of human behaviors in the pandemic. For instance, we report a negative and positive correlation of the frequency change of High-Frequency mutations with the level of international movement controls and the number of flight departures, respectively.

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Section: Discussionmentioning

confidence: 99%

Dynamics of SARS-CoV-2 mutations reveals regional-specificity and similar trends of N501 and High-Frequency mutation N501Y in different levels of control measures

et al. 2021

Preprint

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“…Other mutations of the spike protein fall outside the RBD and are more likely to be involved in the ability to escape from immune recognition (e.g. E484K; [71,72]). Still other mutations are acting on other proteins with unknown effects on the pathogen life-cycle (e.g., compensatory mutations?).…”

Section: Discussionmentioning

confidence: 99%

Multilocus adaptation to vaccination

McLeod

Gandon

2021

Preprint

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Pathogen adaptation to public health interventions, such as vaccination, may take tortuous routes and involve a multitude of genetic mutations acting on distinct phenotypic traits. For example, pathogens can escape the vaccine-induced immune response, or adjust their virulence so as to increase transmission in vaccinated hosts. Despite its importance for public health and vaccine efficacy, how these two adaptations jointly evolve is poorly understood. Taking a trait-centered, rather than variant-centered perspective, here we elucidate the role played by epistasis and recombination, with an emphasis on the different protective effects of vaccination. Vaccines reducing transmission and/or increasing clearance generate positive epistasis between the vaccine-escape and virulence alleles, favouring strains that carry both mutations. Vaccines reducing virulence mortality generate negative epistasis, favouring strains that carry either mutation, but not both. If epistasis is positive, recombination can lead to the sequential fixation of the two mutations and prevent the transient build-up of more virulent escape strains. If epistasis is negative, recombination between loci can create an evolutionary bistability between alternative routes of adaptation, such that whichever adaptation is more accessible tends to be favoured in the long-term. More generally, our model provides a valuable framework for studying pathogen adaptation from a trait-centered view, shifting the focus away from variants.

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“…Among all the protein expressed by the virus, the spike (S) protein directly interacts with the humane ACE2 protein 4 and is the target for vaccines and therapeutics 5 . Thus previous research has been focused on adaptive SARS-CoV-2 mutants on the spike glycoprotein (S), such as D614G, N501Y 6 and E484K 7 . The D614G mutants have a dramatic increase in incidence frequency (IF) and an increased fitness, infectivity and fatality 8–12 .…”

Section: Introductionmentioning

confidence: 99%

“…These rapidly growing lineages all contain D614G, which is associated with the enhanced transmission 23 . Except for D614G, N501Y 6 and E484K 7 , there are other mutants that distinguish these lineages from the original virus. The evaluation of these mutants for functional effects is important.…”

Section: Introductionmentioning

confidence: 99%

Nucleocapsid mutation R203K/G204R increases the infectivity, fitness and virulence of SARS-CoV-2

Xing

Meng

et al. 2021

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In addition to the mutations on the spike protein (S), co-occurring mutations on nucleocapsid (N) protein are also emerging in SARS-CoV-2 world widely. Mutations R203K/G204R on N, carried by high transmissibility SARS-CoV-2 lineages including B.1.1.7 and P.1, has a rapid spread in the pandemic during the past year. In this study, we performed comprehensive population genomic analyses and virology experiment concerning on the evolution, causation and virology consequence of R203K/G204R mutations. The global incidence frequency (IF) of 203K/204R has rose up from nearly zero to 76% to date with a shrinking from August to November in 2020 but bounced later. Our results show that the emergence of B.1.1.7 is associated with the second growth of R203K/G204R mutants. We identified positive selection evidences that support the adaptiveness of 203K/204R variants. The R203K/G204R mutant virus was created and compared with the native virus. The virus competition experiments show that 203K/204R variants possess a replication advantage over the preceding R203/G204 variants, possibly in relation to the ribonucleocapsid (RNP) assemble during the virus replication. Moreover, the 203K/204R virus increased the infectivity in a human lung cell line and induced an enhanced damage to blood vessel of infected hamsters' lungs. In consistence, we observed a positive association between the increased severity of COVID-19 and the IF of 203K/204R from in silicon analysis of global clinical and epidemic data. In combination with the informatics and virology experiment, our work suggested the contribution of 203K/204R to the increased transmission and virulence of the SARS-CoV-2. In addition to mutations on the S protein, the mutations on the N protein are also important to virus spread during the pandemic.

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SARS-CoV-2 spike E484K mutation reduces antibody neutralisation

Cited by 380 publications

References 4 publications

Dynamics of SARS-CoV-2 mutations reveals regional-specificity and similar trends of N501 and High-Frequency mutation N501Y in different levels of control measures

Dynamics of SARS-CoV-2 mutations reveals regional-specificity and similar trends of N501 and High-Frequency mutation N501Y in different levels of control measures

Multilocus adaptation to vaccination

Nucleocapsid mutation R203K/G204R increases the infectivity, fitness and virulence of SARS-CoV-2

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