Early empirical assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020

Leung, Kathy; Shum, Marcus Hh; Leung, Gabriel M.; Lam, Tommy T. Y.; Wu, Joseph T.

doi:10.1101/2020.12.20.20248581

Cited by 26 publications

(17 citation statements)

References 6 publications

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“…27 Originating from N501Y, the last VOC, the year 2020, month 12, variant 01, referred to as SARS-CoV-2 VOC 202012/01 or B.1.1.7, emerged in the UK, containing 23 nucleotide substitutions from the initial SARS-CoV-2. 9,15,[28][29][30] This variant has shown increased transmissibility within the population. 15,31 Furthermore, VOC 202012/01 has a deletion at the position 69/70del that affects the performance of diagnostic polymerase chain reaction (PCR) assays with an S gene target which is not expected to pose a significant concern, as most facilities globally use PCR assays with multiple targets.…”

Section: Variants Of Sars-cov-2mentioning

confidence: 99%

The emerging SARS-CoV-2 variants of concern

Sanyaolu

Okorie

Marinkovic³

et al. 2021

Therapeutic Advances in Infection

102

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Since emerging from Wuhan, China, in December of 2019, the coronavirus (SARS-CoV-2) has been causing devastating severe respiratory infections in humans worldwide. With the disease spreading faster than the medical community could contain it, death tolls increased at an alarming rate worldwide, causing the World Health Organization to officially sanction the SARS-CoV-2 outbreak as a pandemic, leading to a state of worldwide lockdown for the majority of the year 2020. There have been reports of new strains of the virus emerging in various parts of the world, with some strains displaying even greater infectivity and transmissibility. Areas of the emerging variant of concern arise from countries like the United Kingdom, South Africa, Brazil, and India. These mutations carry a lineage from N501Y, D614G, N439K, Y453F, and others, which are globally dominated by clades 20A, 20B, and 20C. This literature review intends to identify and report SARS-CoV-2 variants that are currently evolving and their disease implications.

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Section: Variants Of Sars-cov-2mentioning

confidence: 99%

The emerging SARS-CoV-2 variants of concern

Sanyaolu

Okorie

Marinkovic³

et al. 2021

Therapeutic Advances in Infection

102

View full text Add to dashboard Cite

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“…This is typical for RNA viruses and cannot be automatically interpreted as a sign that the disease it is causing is changing [2], but epidemiological [3] and biochemical [4] data indicate that a viral strain with higher infectivity appeared already in March 2020. Recent pandemic flare ups in the United Kingdom [5] and South Africa [6] suggest that even newer super-transmissible strains are emerging. We can track these events in almost real time thanks to a massive effort in sequencing the SARS-CoV-2 genome variants from all over the world, with most of this information available through resources such as GISAID [1] (https://www.gisaid.org).…”

Section: Introductionmentioning

confidence: 99%

The interplay of SARS-CoV-2 evolution and constraints imposed by the structure and functionality of its proteins

et al. 2021

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The unprecedented pace of the sequencing of the SARS-CoV-2 virus genomes provides us with unique information about the genetic changes in a single pathogen during ongoing pandemic. By the analysis of close to 200,000 genomes we show that the patterns of the SARS-CoV-2 virus mutations along its genome are closely correlated with the structural and functional features of the encoded proteins. Requirements of foldability of proteins’ 3D structures and the conservation of their key functional regions, such as protein-protein interaction interfaces, are the dominant factors driving evolutionary selection in protein-coding genes. At the same time, avoidance of the host immunity leads to the abundance of mutations in other regions, resulting in high variability of the missense mutation rate along the genome. “Unexplained” peaks and valleys in the mutation rate provide hints on function for yet uncharacterized genomic regions and specific protein structural and functional features they code for. Some of these observations have immediate practical implications for the selection of target regions for PCR-based COVID-19 tests and for evaluating the risk of mutations in epitopes targeted by specific antibodies and vaccine design strategies.

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“…mutations are already present in the SARS-CoV-2 population that may weakly affect the interaction with the human receptor, specifically Spike N439K, S477N and N501Y. These mutations are rising in the viral population (>1%) and in particular N501Y is one of the key mutations characterizing lineage B.1.1.7 (Leung et al, 2020), which has seen a recent dramatic increase in frequency in the United Kingdom (Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations -SARS-CoV-2 coronavirus/nCoV-2019 Genomic Epidemiology -Virological , XXXX). Having identified this mutation proves that our combination of targeted mutation frequency and GBPM is a useful pipeline to monitor events in the key region used by SARS-CoV-2 to recognize and enter human bronchial cells.…”

Section: Discussionmentioning

confidence: 99%

“…The rapid increase in frequency of mutation N501Y has been recently observed in the United Kingdom and other countries, as it is one of the variants characterizing lineage B1.1.7 (Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations -SARS-CoV-2 coronavirus/nCoV-2019 Genomic Epidemiology -Virological, 2021). The Asparagine/ Tyrosine substitution in Spike position 501 could contribute to determine an evolutionary advantage for this lineage, based on differential affinity for the human receptor ACE2 (Fratev, 2020;Leung et al, 2020).…”

Section: Mutational Analysis Of Sars-cov-2 Spikementioning

confidence: 99%

Structural genetics of circulating variants affecting the SARS-CoV-2 spike/human ACE2 complex

Ortuso

Mercatelli

Guzzi

et al. 2021

Journal of Biomolecular Structure and Dynamics

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SARS-CoV-2 entry in human cells is mediated by the interaction between the viral Spike protein and the human ACE2 receptor. This mechanism evolved from the ancestor bat coronavirus and is currently one of the main targets for antiviral strategies. However, there currently exist several Spike protein variants in the SARS-CoV-2 population as the result of mutations, and it is unclear if these variants may exert a specific effect on the affinity with ACE2 which, in turn, is also characterized by multiple alleles in the human population. In the current study, the GBPM analysis, originally developed for highlighting host-guest interaction features, has been applied to define the key amino acids responsible for the Spike/ACE2 molecular recognition, using four different crystallographic structures. Then, we intersected these structural results with the current mutational status, based on more than 295,000 sequenced cases, in the SARS-CoV-2 population. We identified several Spike mutations interacting with ACE2 and mutated in at least 20 distinct patients: S477N, N439K, N501Y, Y453F, E484K, K417N, S477I and G476S. Among these, mutation N501Y in particular is one of the events characterizing SARS-CoV-2 lineage B.1.1.7, which has recently risen in frequency in Europe. We also identified five ACE2 rare variants that may affect interaction with Spike and susceptibility to infection: S19P, E37K, M82I, E329G and G352V.

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Early empirical assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020

Cited by 26 publications

References 6 publications

The emerging SARS-CoV-2 variants of concern

The emerging SARS-CoV-2 variants of concern

The interplay of SARS-CoV-2 evolution and constraints imposed by the structure and functionality of its proteins

Structural genetics of circulating variants affecting the SARS-CoV-2 spike/human ACE2 complex

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