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Michael Novakhov – SharedNewsLinks℠: The D614G mutation of SARS-CoV-2 spike protein enhances viral infectivity and decreases neutralization sensitivity to individual convalescent sera | bioRxiv



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

Jie Hu, Chang-Long He, Qing-Zhu Gao, Gui-Ji Zhang, Xiao-Xia Cao, Quan-Xin Long, Hai-Jun Deng, Lu-Yi Huang, Juan Chen, Kai Wang, Ni Tang, Ai-Long Huang
Jie Hu

1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China

Chang-Long He

1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China

Qing-Zhu Gao

1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China

Gui-Ji Zhang

1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China

Xiao-Xia Cao

1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China

Lu-Yi Huang

1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China

Juan Chen

1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China

Kai Wang

1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China

Ni Tang

1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China

Ai-Long Huang

1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China

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.

Michael Novakhov – SharedNewsLinks℠