The D614G mutation of SARS-CoV-2 spike protein enhances viral infectivity and decreases neutralization sensitivity to individual convalescent sera

The D614G mutation of SARS-CoV-2 spike protein enhances viral infectivity and decreases neutralization sensitivity to individual convalescent seraJie Hu, Chang-Long He, Qing-Zhu Gao, Gui-Ji Zhang, Xiao-Xia Cao, Quan-Xin Long, Hai-Jun Deng, Lu-Yi Huang, Juan Chen, View ORCID ProfileKai Wang, Ni Tang, Ai-Long Huang
doi: https://doi.org/10.1101/2020.06.20.161323
Abstract
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike protein that mediates SARS-CoV-2 entry into host cells, is one of the major targets for vaccines and therapeutics. Thus, insights into the sequence variations of S protein are key to understanding the infection and antigenicity of SARS-CoV-2. Here, we observed a dominant mutational variant at the 614 position of S protein (aspartate to glycine, D614G mutation). Using pseudovirus-based assay, we found 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 the S-D614 pseudovirus, Moreover, 93% (38/41) sera from convalescent COVID-19 patients could neutralize both S-D614 and S-G614 pseudotyped viruses with comparable efficiencies, but about 7% (3/41) convalescent sera showed decreased neutralizing activity against S-G614 pseudovirus. These findings have important implications for SARS-CoV-2 transmission and immune interventions.

Competing Interest Statement
The authors have declared no competing interest.
Full paper here
https://www.biorxiv.org/content/10.1101/2020.06.20.161323v1