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 246 publications

(166 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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“…30 Highly contagious Delta (B.1.617.2) variant compared to the previous SARS-CoV-2 variants contained the P681R mutation at the S1/S2 cleavage site. 31,32 The Delta variant containing P681R mutation augmented the cleavage of S protein into S1 and S2, thereby upregulating the viral replication in the in vitro respiratory models.…”

Section: Natural Mutations At and Near Fcs And Their Effectsmentioning

confidence: 99%

Roles of the polybasic furin cleavage site of spike protein in SARS‐CoV‐2 replication, pathogenesis, and host immune responses and vaccination

Hossain

Tang

Akter

et al. 2021

Journal of Medical Virology

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The polybasic furin cleavage site insertion with four amino acid motifs (PRRA) in spike protein's S1/S2 junction site is important in determining viral infectivity, transmission, and host range. However, there is no review so far explaining the effect of the furin cleavage site of the spike protein on SARS-CoV-2 replication and pathogenesis in the host and immune responses and vaccination. Therefore, here we specifically focused on genomic evolution and properties of the cleavage site of spike protein in the context of SARS-CoV-2 followed by its effect on viral entry, replication, and pathogenesis. We also explored whether the spike protein furin cleavage site affected the host immune responses and SARS-CoV-2 vaccination. This review will help to provide novel insights into the effects of polybasic furin cleavage site on the current COVID-19 pandemic.

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

Cited by 246 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

Roles of the polybasic furin cleavage site of spike protein in SARS‐CoV‐2 replication, pathogenesis, and host immune responses and vaccination

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