RT Journal Article
SR Electronic
T1 D614G mutation of SARS-CoV-2 spike protein enhances viral infectivity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.20.161323
DO 10.1101/2020.06.20.161323
A1 Jie Hu
A1 Chang-Long He
A1 Qing-Zhu Gao
A1 Gui-Ji Zhang
A1 Xiao-Xia Cao
A1 Quan-Xin Long
A1 Hai-Jun Deng
A1 Lu-Yi Huang
A1 Juan Chen
A1 Kai Wang
A1 Ni Tang
A1 Ai-Long Huang
YR 2020
UL http://biorxiv.org/content/early/2020/07/06/2020.06.20.161323.abstract
AB Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike (S) protein that mediates SARS-CoV-2 entry into host cells is a major target for vaccines and therapeutics. Thus, insights into its sequence variations are key to understanding the infection and antigenicity of SARS-CoV-2. A dominant mutational variant at position 614 of the S protein (aspartate to glycine, D614G mutation) was observed in the SARS-CoV-2 genome sequence obtained from the Nextstrain database. Using a pseudovirus-based assay, we identified that S-D614 and S-G614 protein pseudotyped viruses share a common receptor, human angiotensin-converting enzyme 2 (ACE2), which could be blocked by recombinant ACE2 with the fused Fc region of human IgG1. However, S-D614 and S-G614 protein demonstrated functional differences. First, S-G614 protein could be cleaved by serine protease elastase-2 more efficiently. Second, S-G614 pseudovirus infected 293T-ACE2 cells significantly more efficiently than did the S-D614 pseudovirus, especially in the presence of elastase-2. Third, an elastase inhibitor approved for clinical use blocked elastase-enhanced S-G614 pseudovirus infection. Moreover, 93% (65/70) convalescent sera from patients with COVID-19 could neutralize both S-D614 and S-G614 pseudoviruses with comparable efficiencies, but about 7% (5/70) convalescent sera showed reduced neutralizing activity against the S-G614 pseudovirus. These findings have important implications for SARS-CoV-2 transmission and immune interventions.Competing Interest StatementThe authors have declared no competing interest.