SARS-CoV-2 spike D614G change enhances replication and transmission

Zhou, Bin; Thao, Tran Thi Nhu; Hoffmann, Donata; Taddeo, Adriano; Ebert, Nadine; Labroussaa, Fabien; Pohlmann, Anne; King, Jacqueline; Steiner, Silvio; Kelly, Jenna N.; Portmann, Jasmine; Halwe, Nico Joel; Ulrich, Lisa K.; Trüeb, Bettina Salome; Fan, Xiaoyu; Hoffmann, Bernd; Wang, Li; Thomann, Andreas; Lin, Xudong; Stalder, Hanspeter; Pozzi, Berta; Brot, Simone de; Jiang, Nannan; Cui, Dan; Hossain, Jaber; Wilson, Malania M.; Keller, Matthew W.; Stark, Thomas; Barnes, John; Dijkman, Ronald; Jores, Joerg; Benarafa, Charaf; Wentworth, David E.; Thiel, Volker; Beer, Martin

doi:10.1038/s41586-021-03361-1

Cited by 487 publications

(468 citation statements)

References 28 publications

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“…1 ABC). Among these positions is the nucleotide substitution of A to C at site 23403, which is responsible for the D614G mutation in the spike protein that has been associated with increased transmissibility 16–18 . Of the over half a million complete, human-derived SARS-CoV-2 strains available on GISAID as of February 16, 2021, fewer than 0.5% of genomes differed from the 14 clades’ cdSNP profiles by more than one nucleotide.…”

Section: Resultsmentioning

confidence: 99%

Recombinant SARS-CoV-2 genomes are currently circulating at low levels

VanInsberghe

Neish

Lowen

et al. 2020

Preprint

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Viral recombination has the potential to bring about viral genotypes with modified phenotypic characteristics, including transmissibility and virulence. Although the capacity for recombination among Betacoronaviruses is well documented, SARS-CoV-2 has only been circulating in humans for approximately 8 months and thus has had a relatively short window of opportunity for the occurrence of recombination. The ability to detect recombination has further been limited by the relatively low levels of genetic diversity in SARS-CoV-2. Despite this, two studies have reported recombinants among SARS-CoV-2 strains. Here we first revisit these findings with a new analysis approach, arguing that neither presents a clear case of within-SARS-CoV-2 recombination. Applying this same approach to available SARS-CoV-2 sequences, we then identify five recombinant genomes. Each of these genomes contain phylogenetic markers of two distinct SARS-CoV-2 clades. Further, the predicted parent clades of these recombinant genomes were, with one exception, documented to be co-circulating in the country of infection in the two weeks prior to the sample being collected. Our results indicate that recombination among SARS-CoV-2 strains is occurring, but is either not widespread or often remains undetectable given current levels of viral genetic diversity. Efforts to monitor the emergence of new recombinant genomes should therefore be sustained.

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Section: Resultsmentioning

confidence: 99%

Recombinant SARS-CoV-2 genomes are currently circulating at low levels

VanInsberghe

Neish

Lowen

et al. 2020

Preprint

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“…The B.1.1.7, B.1.351, and P.1 lineages all harbor a N501Y mutation in the RBD which increases the affinity for the ACE2 receptor (57,58), and a D614G mutation which mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection increases virion spike density, infectivity and transmissibility (59,60). The B.1.351 and P.1 lineages also share the E484K mutations in the RBD and both variants are mutated at 417 (K417T in P.1).…”

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confidence: 99%

mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection

Stamatatos

Czartoski

Wan

et al. 2021

Science

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Emerging SARS-CoV-2 variants have raised concerns about resistance to neutralizing antibodies elicited by previous infection or vaccination. We examined whether sera from recovered and naïve donors collected prior to, and following immunizations with existing mRNA vaccines, could neutralize the Wuhan-Hu-1 and B.1.351 variants. Pre-vaccination sera from recovered donors neutralized Wuhan-Hu-1 and sporadically neutralized B.1.351, but a single immunization boosted neutralizing titers against all variants and SARS-CoV-1 by up to 1000-fold. Neutralization was due to antibodies targeting the receptor binding domain and was not boosted by a second immunization. Immunization of naïve donors also elicited cross-neutralizing responses, but at lower titers. Our study highlights the importance of vaccinating both uninfected and previously infected persons to elicit cross-variant neutralizing antibodies.

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“…In vivo studies with authentic SARS-CoV-2 further showed that D614G enhances replication and transmission. [283][284][285][286][287][288][289][290]. During the second wave of the pandemic (end of 2020/early 2021), new SARS-CoV-2 variants emerged, subsequently replacing old variants [291].…”

Section: Sars-cov-2 Mutates On a Low But Constant Level Yielding Mutant Variants Over Timementioning

confidence: 99%

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

Duerr¹,

Jimenez²,

Dittmann³

2021

Preprint

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SARS-CoV-2 and HIV are zoonotic viruses that rapidly reached pandemic scale causing global losses and fear. The COVID-19 and AIDS pandemics ignited massive efforts worldwide to develop antiviral strategies and characterize viral architectures, biological and immunological properties, and clinical outcomes. Although both viruses have a comparable appearance as enveloped, positive-stranded RNA viruses with envelope spikes mediating cellular entry, the entry process, downstream biological and immunological pathways, clinical outcomes, and disease courses are strikingly different. This review provides a systemic comparison of both viruses’ structural and functional characteristics delineating their distinct strategies for efficient spread.

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SARS-CoV-2 spike D614G change enhances replication and transmission

Cited by 487 publications

References 28 publications

Recombinant SARS-CoV-2 genomes are currently circulating at low levels

Recombinant SARS-CoV-2 genomes are currently circulating at low levels

mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

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