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Journal ArticleDOI

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

TL;DR: Investigation of the hypothesis for positive selection of Spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage.
About: This article is published in Cell.The article was published on 2021-01-07 and is currently open access. It has received 770 citations till now. The article focuses on the topics: Population.
Citations
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Journal ArticleDOI
TL;DR: A review of the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure is presented in this article.
Abstract: Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. Since late 2020, however, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations, in the context of ‘variants of concern’, that impact virus characteristics, including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. There is emerging evidence of reduced neutralization of some SARS-CoV-2 variants by postvaccination serum; however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Nonetheless, manufacturers are preparing platforms for a possible update of vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is done alongside experiments to elucidate the phenotypic impacts of mutations. In this Review, we summarize the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets. The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been characterized by the emergence of mutations and so-called variants of concern that impact virus characteristics, including transmissibility and antigenicity. In this Review, members of the COVID-19 Genomics UK (COG-UK) Consortium and colleagues summarize mutations of the SARS-CoV-2 spike protein, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets.

2,047 citations

Journal ArticleDOI
15 Apr 2021-Nature
TL;DR: A newly arisen lineage of SARS-CoV-2 (designated 501Y.V2) was identified in South Africa after the first wave of the epidemic in a severely affected metropolitan area (Nelson Mandela Bay) that is located on the coast of the Eastern Cape province.
Abstract: Continued uncontrolled transmission of SARS-CoV-2 in many parts of the world is creating conditions for substantial evolutionary changes to the virus1,2. Here we describe a newly arisen lineage of SARS-CoV-2 (designated 501Y.V2; also known as B.1.351 or 20H) that is defined by eight mutations in the spike protein, including three substitutions (K417N, E484K and N501Y) at residues in its receptor-binding domain that may have functional importance3-5. This lineage was identified in South Africa after the first wave of the epidemic in a severely affected metropolitan area (Nelson Mandela Bay) that is located on the coast of the Eastern Cape province. This lineage spread rapidly, and became dominant in Eastern Cape, Western Cape and KwaZulu-Natal provinces within weeks. Although the full import of the mutations is yet to be determined, the genomic data-which show rapid expansion and displacement of other lineages in several regions-suggest that this lineage is associated with a selection advantage that most plausibly results from increased transmissibility or immune escape6-8.

1,171 citations

Journal ArticleDOI
Nuno R. Faria, Thomas A. Mellan1, Charles Whittaker1, Ingra Morales Claro2, Darlan da Silva Candido2, Darlan da Silva Candido3, Swapnil Mishra1, Myuki A E Crispim, Flavia C. S. Sales2, Iwona Hawryluk1, John T. McCrone4, Ruben J.G. Hulswit3, Lucas A M Franco2, Mariana S. Ramundo2, Jaqueline Goes de Jesus2, Pamela S Andrade2, Thais M. Coletti2, Giulia M. Ferreira5, Camila A. M. Silva2, Erika R. Manuli2, Rafael Henrique Moraes Pereira, Pedro S. Peixoto2, Moritz U. G. Kraemer3, Nelson Gaburo, Cecilia da C. Camilo, Henrique Hoeltgebaum1, William Marciel de Souza2, Esmenia C. Rocha2, Leandro Marques de Souza2, Mariana C. Pinho2, Leonardo José Tadeu de Araújo6, Frederico S V Malta, Aline B. de Lima, Joice do P. Silva, Danielle A G Zauli, Alessandro C. S. Ferreira, Ricardo P Schnekenberg3, Daniel J Laydon1, Patrick G T Walker1, Hannah M. Schlüter1, Ana L. P. dos Santos, Maria S. Vidal, Valentina S. Del Caro, Rosinaldo M. F. Filho, Helem M. dos Santos, Renato Santana Aguiar7, José Luiz Proença-Módena8, Bruce Walker Nelson9, James A. Hay10, Melodie Monod1, Xenia Miscouridou1, Helen Coupland1, Raphael Sonabend1, Michaela A. C. Vollmer1, Axel Gandy1, Carlos A. Prete2, Vitor H. Nascimento2, Marc A. Suchard11, Thomas A. Bowden3, Sergei L Kosakovsky Pond12, Chieh-Hsi Wu13, Oliver Ratmann1, Neil M. Ferguson1, Christopher Dye3, Nicholas J. Loman14, Philippe Lemey15, Andrew Rambaut4, Nelson Abrahim Fraiji, Maria Perpétuo Socorro Sampaio Carvalho, Oliver G. Pybus16, Oliver G. Pybus3, Seth Flaxman1, Samir Bhatt17, Samir Bhatt1, Ester Cerdeira Sabino2 
21 May 2021-Science
TL;DR: In this article, the authors used a two-category dynamical model that integrates genomic and mortality data to estimate that P.1 may be 1.7-to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.
Abstract: Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.

985 citations

Posted ContentDOI
22 Dec 2020-medRxiv
TL;DR: In this paper, the authors describe a new SARS-CoV-2 lineage (501Y.V2) characterised by eight lineage-defining mutations in the spike protein, including three at important residues in the receptor-binding domain (K417N, E484K and N501Y).
Abstract: Summary Continued uncontrolled transmission of the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in many parts of the world is creating the conditions for significant virus evolution. Here, we describe a new SARS-CoV-2 lineage (501Y.V2) characterised by eight lineage-defining mutations in the spike protein, including three at important residues in the receptor-binding domain (K417N, E484K and N501Y) that may have functional significance. This lineage emerged in South Africa after the first epidemic wave in a severely affected metropolitan area, Nelson Mandela Bay, located on the coast of the Eastern Cape Province. This lineage spread rapidly, becoming within weeks the dominant lineage in the Eastern Cape and Western Cape Provinces. Whilst the full significance of the mutations is yet to be determined, the genomic data, showing the rapid displacement of other lineages, suggest that this lineage may be associated with increased transmissibility.

980 citations

Journal ArticleDOI
29 Oct 2020-Cell
TL;DR: It is shown that D614G was more infectious than the ancestral form on human lung cells, colon cells, and on cells rendered permissive by ectopic expression of human ACE2 or of ACE2 orthologs from various mammals, including Chinese rufous horseshoe bat and Malayan pangolin.

840 citations

References
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Journal ArticleDOI
TL;DR: UNLABELLED Analysis of Phylogenetics and Evolution (APE) is a package written in the R language for use in molecular evolution and phylogenetics that provides both utility functions for reading and writing data and manipulating phylogenetic trees.
Abstract: Summary: Analysis of Phylogenetics and Evolution (APE) is a package written in the R language for use in molecular evolution and phylogenetics. APE provides both utility functions for reading and writing data and manipulating phylogenetic trees, as well as several advanced methods for phylogenetic and evolutionary analysis (e.g. comparative and population genetic methods). APE takes advantage of the many R functions for statistics and graphics, and also provides a flexible framework for developing and implementing further statistical methods for the analysis of evolutionary processes. Availability: The program is free and available from the official R package archive at http://cran.r-project.org/src/contrib/PACKAGES.html#ape. APE is licensed under the GNU General Public License.

10,818 citations


"Evaluating the Effects of SARS-CoV-..." refers methods in this paper

  • ...Rooted and dated phylogenies were estimated by randomly resolving polytomies in the ML trees described above using ape 5.3(Paradis et al., 2004) and treedater 0.5.1(Volz and Frost, 2017)....

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Journal ArticleDOI
03 Feb 2020-Nature
TL;DR: Phylogenetic and metagenomic analyses of the complete viral genome of a new coronavirus from the family Coronaviridae reveal that the virus is closely related to a group of SARS-like coronaviruses found in bats in China.
Abstract: Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1–3. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans. Phylogenetic and metagenomic analyses of the complete viral genome of a new coronavirus from the family Coronaviridae reveal that the virus is closely related to a group of SARS-like coronaviruses found in bats in China.

9,231 citations


"Evaluating the Effects of SARS-CoV-..." refers background in this paper

  • ...This shows the early stages of emergence of D614G into Europe from China....

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  • ...Retrospectively sampled viruses suggest this mutation was present in Guangzhou, Sichuan, and Shanghai Provinces, China in late January (Figure S1)....

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  • ...We included the first sequenced genome of SARS-CoV-2 from China (Wu et al., 2020) as an outgroup to root the tree....

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  • ...It is therefore likely that the D614G mutation occurred in China before being introduced on multiple occasions to European countries (Lai et al., 2020) where it increased in frequency....

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Journal ArticleDOI
TL;DR: A new statistical method for estimating divergence dates of species from DNA sequence data by a molecular clock approach is developed, and this dating may pose a problem for the widely believed hypothesis that the bipedal creatureAustralopithecus afarensis, which lived some 3.7 million years ago, was ancestral to man and evolved after the human-ape splitting.
Abstract: A new statistical method for estimating divergence dates of species from DNA sequence data by a molecular clock approach is developed. This method takes into account effectively the information contained in a set of DNA sequence data. The molecular clock of mitochondrial DNA (mtDNA) was calibrated by setting the date of divergence between primates and ungulates at the Cretaceous-Tertiary boundary (65 million years ago), when the extinction of dinosaurs occurred. A generalized least-squares method was applied in fitting a model to mtDNA sequence data, and the clock gave dates of 92.3 +/- 11.7, 13.3 +/- 1.5, 10.9 +/- 1.2, 3.7 +/- 0.6, and 2.7 +/- 0.6 million years ago (where the second of each pair of numbers is the standard deviation) for the separation of mouse, gibbon, orangutan, gorilla, and chimpanzee, respectively, from the line leading to humans. Although there is some uncertainty in the clock, this dating may pose a problem for the widely believed hypothesis that the pipedal creature Australopithecus afarensis, which lived some 3.7 million years ago at Laetoli in Tanzania and at Hadar in Ethiopia, was ancestral to man and evolved after the human-ape splitting. Another likelier possibility is that mtDNA was transferred through hybridization between a proto-human and a proto-chimpanzee after the former had developed bipedalism.

8,124 citations


"Evaluating the Effects of SARS-CoV-..." refers methods in this paper

  • ...Nucleotide evolution was modeled as a strict clock HKY process (Hasegawa et al., 1985)....

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  • ...The HKY model was used to model nucleotide evolution(Hasegawa et al., 1985), and, following Duchene et al....

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Journal ArticleDOI
01 Apr 2020-Nature
TL;DR: Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract.
Abstract: Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity—but also aided in the control—of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6–8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples—in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19. Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract.

5,840 citations


"Evaluating the Effects of SARS-CoV-..." refers background in this paper

  • ...Combined with epidemiological observations of disparities in viral loads in the upper respiratory tract (Lorenzo-Redondo et al., 2020; Wölfel et al., 2020), these results are suggestive of a transmission-mediated fitness differential between spike 614 variants....

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Journal ArticleDOI
TL;DR: The software package Tracer is presented, for visualizing and analyzing the MCMC trace files generated through Bayesian phylogenetic inference, which provides kernel density estimation, multivariate visualization, demographic trajectory reconstruction, conditional posterior distribution summary, and more.
Abstract: Bayesian inference of phylogeny using Markov chain Monte Carlo (MCMC) plays a central role in understanding evolutionary history from molecular sequence data. Visualizing and analyzing the MCMC-generated samples from the posterior distribution is a key step in any non-trivial Bayesian inference. We present the software package Tracer (version 1.7) for visualizing and analyzing the MCMC trace files generated through Bayesian phylogenetic inference. Tracer provides kernel density estimation, multivariate visualization, demographic trajectory reconstruction, conditional posterior distribution summary, and more. Tracer is open-source and available at http://beast.community/tracer.

5,492 citations


"Evaluating the Effects of SARS-CoV-..." refers methods in this paper

  • ...Convergence was assessed using Tracer(Rambaut et al., 2018) prior to further analysis....

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  • ...10.5 (Suchard et al., 2018) https://beast.community/ Tracer (Rambaut et al., 2018) https://beast.community/ BEAST2 PhyDyn (Bouckaert et al., 2019; Volz and Siveroni, 2018) https://github.com/mrc-ide/PhyDyn ARTIC network protocol ARTIC network https://artic.network/ncov-2019 R packages (treedater 0.5.1, ape package v. 5.3, brms v. 2.13.5, rstan v. 2.21.2, SPIn v. 1.1, skygrowth 0.3.1) (Paradis and Schliep, 2019; Volz and Frost, 2017; Bürkner, 2018; Stan Development Team, 2020; Liu et al., 2015; Volz and Didelot, 2018) http://www.R-project.org; https://github.com/mrc-ide/skygrowth IQtree 1.6.12 (Minh et al., 2020; Rambaut et al., 2020) http://www.iqtree.org/ MRC-CLIMB (Connor et al., 2016) https://www.climb.ac.uk/ Nextflow pipeline for processing/ assembly of ARTIC protocol amplicons https://github.com/connor-lab/ncov2019artic-nf https://github.com/connor-lab/ ncov2019-artic-nf...

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