Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant

Liu, Yang; Liu, Jianying; Johnson, Bryan A.; Xia, Hongjie; Ku, Zhiqiang; Schindewolf, Craig; Widen, Steven G.; An, Zhiqiang; Weaver, Scott C.; Menachery, Vineet D.; Xie, Xuping; Shi, Pei–Yong

doi:10.1016/j.celrep.2022.110829

Cited by 280 publications

(254 citation statements)

References 38 publications

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“…Three more out of these 13 mutations were in 3′ or 5′ UTRs. One of these common mutations during third peak, S:P681R placed at a fur in cleavage position that separates the spike 1 (S1) and S2 subunits is known to increase infectivity of the Delta variant via cell surface entry ( 20 ). Similarly, the other most common mutation during third peak viz.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Lineage Tracking, and Evolving Trends Seen during Three Consecutive Peaks of Infection in Delhi, India: a Clinico-Genomic Study

et al. 2022

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Lineage Tracking, and Evolving Trends Seen during Three Consecutive Peaks of Infection in Delhi, India: a Clinico-Genomic Study

et al. 2022

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“…Two independent mutations that create an advantageous effect at a conserved position, but with different amino acid substitutions, are S:P681H and S:P681R, occurring in Alpha and Delta, respectively (Liu et al . 2021 ; Mohammad, Abubaker and Al-Mulla 2021 ). Both were created by a change of the nucleotide at c23604 (to 23604a in Alpha and to 23604g in Delta).…”

Section: Comparing Three Widely Spread Vocsmentioning

confidence: 99%

“…A synthetic construct of a Delta genome with the complete spike protein from Alpha displayed decreased fitness toward human cells in vitro compared with Delta, and compared with Alpha, suggesting that the spike protein of Delta is better equipped for its own genetic background than the spike of Alpha is (Liu et al . 2021 ). The role of S:P681R in enhanced furin sensitivity is currently being debated (Zhang et al .…”

Section: Comparing Three Widely Spread Vocsmentioning

confidence: 99%

The first three waves of the Covid-19 pandemic hint at a limited genetic repertoire for SARS-CoV-2

Wassenaar

Wanchai

Buzard³

et al. 2022

FEMS Microbiology Reviews

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The genomic diversity of SARS-CoV-2 is the result of a relatively low level of spontaneous mutations introduced during viral replication. With millions of SARS-CoV-2 genome sequences now available, we can begin to assess the overall genetic repertoire of this virus. We find that during 2020 there was a global wave of one variant that went largely unnoticed, possibly because its members were divided over several sub-lineages (B.1.177 and sub-lineages B.1.177.XX). We collectively call this Janus, and it was eventually replaced by the Alpha (B.1.1.7) Variant of Concern (VoC), next replaced by Delta (B.1.617.2), which itself might soon be replaced by a fourth pandemic wave consisting of Omicron (B.1.1.529). We observe that splitting up and redefining variant lineages over time, as was the case with Janus and is now happening with Alpha, Delta, and Omicron, is not helpful to describe the epidemic waves spreading globally. Only about five percent of the 30,000 nucleotides of the SARS-CoV-2 genome are found to be variable. We conclude that a fourth wave of the pandemic with the Omicron variant might not be that different from other VoCs, and that we may already have the tools in hand to effectively deal with this new VoC.

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“…P681R locates at the furin cleavage site between S1/S2 and is unique to the B.1.617 lineage. It has been shown to increase infection via cell surface entry and cause higher pathogenicity by facilitating S1/S2 cleavage and enhancing viral fusogenicity by over 100% (Liu et al, 2021a; Saito et al, 2022). Despite the efforts in elucidating the impact of the Delta variant’s mutations on host recognition and immune evasion using recombinant proteins, the architecture of the authentic virus, the in situ structure of its proteins, and distribution of its antigens remain elusive.…”

Section: Introductionmentioning

confidence: 99%

In situ architecture and membrane fusion of SARS-CoV-2 Delta variant

Song

Yao

et al. 2022

Preprint

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SUMMARYAmong the current five Variants of Concern, infections caused by the SARS-CoV-2 B.1.617.2 (Delta) variant are often associated with the greatest severity. Despite recent advances on the molecular basis of elevated pathogenicity using recombinant proteins, architecture of intact Delta virions remains veiled. Moreover, the detailed mechanism of S-mediated membrane fusion remains elusive. Here we report the molecular assembly and fusion snapshots of the authentic Delta variant. Envelope invagination and fusion events were frequently observed. Native structures of pre- and postfusion S were determined up to 4.1-Å resolution. Site-specific glycan analysis revealed increased oligomannose-type glycosylation of native Delta S over that of the Wuhan-Hu-1 S. Based on these findings, we proposed a model for S-mediated membrane fusion and a model for the invagination formation.In BriefCryo-ET of intact SARS-CoV-2 Delta variant revealed its unique architecture and captured snapshots of its membrane fusion in action.

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Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant

Cited by 280 publications

References 38 publications

SARS-CoV-2 Lineage Tracking, and Evolving Trends Seen during Three Consecutive Peaks of Infection in Delhi, India: a Clinico-Genomic Study

SARS-CoV-2 Lineage Tracking, and Evolving Trends Seen during Three Consecutive Peaks of Infection in Delhi, India: a Clinico-Genomic Study

The first three waves of the Covid-19 pandemic hint at a limited genetic repertoire for SARS-CoV-2

In situ architecture and membrane fusion of SARS-CoV-2 Delta variant

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