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Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation

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Abstract

During the current SARS-CoV-2 pandemic, a variety of mutations have accumulated in the viral genome, and currently, four variants of concern (VOCs) are considered potentially hazardous to human society1. The recently emerged B.1.617.2/Delta VOC is closely associated with the COVID-19 surge that occurred in India in the spring of 20212. However, its virological properties remain unclear. Here, we show that the B.1.617.2/Delta variant is highly fusogenic and notably more pathogenic than prototypic SARS-CoV-2 in infected hamsters. The P681R mutation in the spike protein, which is highly conserved in this lineage, facilitates spike protein cleavage and enhances viral fusogenicity. Moreover, we demonstrate that the P681R-bearing virus exhibits higher pathogenicity than its parental virus. Our data suggest that the P681R mutation is a hallmark of the virological phenotype of the B.1.617.2/Delta variant and is associated with enhanced pathogenicity.

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Correspondence to Shinya Tanaka, So Nakagawa, Terumasa Ikeda, Takasuke Fukuhara, Yoshihiro Kawaoka or Kei Sato.

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This file contains Supplementary Fig. 1: Gating strategy for flow cytometry of S protein expressing cells; and Supplementary Fig. 2: Original (uncrossed) blots.

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Supplementary Table 1

Number of daily deposited sequences in GISAID.

Supplementary Table 2

Percentage of the mutations detected in the S protein of the B.1.617 lineage.

Supplementary Table 3

The SARS-CoV-2 genomic region encoded by each template and the primers used for the preparation of each fragment for CPER.

Supplementary Table 4

Summary of the viral sequences used in this study.

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Saito, A., Irie, T., Suzuki, R. et al. Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation. Nature (2021). https://doi.org/10.1038/s41586-021-04266-9

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