TY - JOUR T1 - Naturally mutated spike proteins of SARS-CoV-2 variants show differential levels of cell entry JF - bioRxiv DO - 10.1101/2020.06.15.151779 SP - 2020.06.15.151779 AU - Seiya Ozono AU - Yanzhao Zhang AU - Hirotaka Ode AU - Toong Seng Tan AU - Kazuo Imai AU - Kazuyasu Miyoshi AU - Satoshi Kishigami AU - Takamasa Ueno AU - Yasumasa Iwatani AU - Tadaki Suzuki AU - Kenzo Tokunaga Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/06/26/2020.06.15.151779.abstract N2 - The causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is steadily mutating during continuous transmission among humans. Such mutations can occur in the spike (S) protein that binds to the angiotensin-converting enzyme-2 (ACE2) receptor and is cleaved by transmembrane protease serine 2 (TMPRSS2). However, whether S mutations affect SARS-CoV-2 infectivity remains unknown. Here, we show that naturally occurring S mutations can reduce or enhance cell entry via ACE2 and TMPRSS2. A SARS-CoV-2 S-pseudotyped lentivirus exhibits substantially lower entry than SARS-CoV S. Among S variants, the D614G mutant shows the highest cell entry, as supported by structural observations. Nevertheless, the D614G mutant remains susceptible to neutralization by antisera against prototypic viruses. Taken together, these data indicate that the D614G mutation enhances viral infectivity while maintaining neutralization susceptibility.Competing Interest StatementThe authors have declared no competing interest. ER -