%0 Journal Article %A Akatsuki Saito %A Hesham Nasser %A Keiya Uriu %A Yusuke Kosugi %A Takashi Irie %A Kotaro Shirakawa %A Kenji Sadamasu %A Izumi Kimura %A Jumpei Ito %A Jiaqi Wu %A Seiya Ozono %A Kenzo Tokunaga %A Erika P Butlertanaka %A Yuri L Tanaka %A Ryo Shimizu %A Kenta Shimizu %A Takasuke Fukuhara %A Ryoko Kawabata %A Takemasa Sakaguchi %A Isao Yoshida %A Hiroyuki Asakura %A Mami Nagashima %A Kazuhisa Yoshimura %A Yasuhiro Kazuma %A Ryosuke Nomura %A Yoshihito Horisawa %A Akifumi Takaori-Kondo %A The Genotype to Phenotype Japan (G2P-Japan) Consortium %A So Nakagawa %A Terumasa Ikeda %A Kei Sato %T SARS-CoV-2 spike P681R mutation enhances and accelerates viral fusion %D 2021 %R 10.1101/2021.06.17.448820 %J bioRxiv %P 2021.06.17.448820 %X During the current SARS-CoV-2 pandemic, a variety of mutations have been accumulated in the viral genome, and at least five variants of concerns (VOCs) have been considered as the hazardous SARS-CoV-2 variants to the human society. The newly emerging VOC, the B.1.617.2 lineage (delta variant), closely associates with a huge COVID-19 surge in India in Spring 2021. However, its virological property remains unclear. Here, we show that the B.1.617 variants are highly fusogenic and form prominent syncytia. Bioinformatic analyses reveal that the P681R mutation in the spike protein is highly conserved in this lineage. Although the P681R mutation decreases viral infectivity, this mutation confers the neutralizing antibody resistance. Notably, we demonstrate that the P681R mutation facilitates the furin-mediated spike cleavage and enhances and accelerates cell-cell fusion. Our data suggest that the P681R mutation is a hallmark characterizing the virological phenotype of this newest VOC, which may associate with viral pathogenicity.HighlightsP681R mutation is highly conserved in the B.1.617 lineagesP681R mutation accelerates and enhances SARS-CoV-2 S-mediated fusionPromotion of viral fusion by P681R mutation is augmented by TMPRSS2Competing Interest StatementThe authors have declared no competing interest. %U https://www.biorxiv.org/content/biorxiv/early/2021/06/17/2021.06.17.448820.full.pdf