RT Journal Article SR Electronic T1 Naturally mutated spike proteins of SARS-CoV-2 variants show differential levels of cell entry JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.06.15.151779 DO 10.1101/2020.06.15.151779 A1 Seiya Ozono A1 Yanzhao Zhang A1 Hirotaka Ode A1 Tan Toong Seng A1 Kazuo Imai A1 Kazuyasu Miyoshi A1 Satoshi Kishigami A1 Takamasa Ueno A1 Yasumasa Iwatani A1 Tadaki Suzuki A1 Kenzo Tokunaga YR 2020 UL http://biorxiv.org/content/early/2020/06/15/2020.06.15.151779.abstract AB 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 viral 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.