SARS-CoV-2 D614G spike mutation increases entry efficiency with enhanced ACE2-binding affinity

Seiya Ozono, Yanzhao Zhang, Hirotaka Ode, Kaori Sano, Toong Seng Tan, Kazuo Imai, Kazuyasu Miyoshi, Satoshi Kishigami, Takamasa Ueno, Yasumasa Iwatani, Tadaki Suzuki and Kenzo Tokunaga ()
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Seiya Ozono: National Institute of Infectious Diseases
Yanzhao Zhang: National Institute of Infectious Diseases
Hirotaka Ode: National Hospital Organization Nagoya Medical Center
Kaori Sano: National Institute of Infectious Diseases
Toong Seng Tan: Joint Research Center for Human Retrovirus Infection
Kazuo Imai: Self-Defense Forces Central Hospital
Kazuyasu Miyoshi: Self-Defense Forces Central Hospital
Satoshi Kishigami: University of Yamanashi
Takamasa Ueno: Joint Research Center for Human Retrovirus Infection
Yasumasa Iwatani: National Hospital Organization Nagoya Medical Center
Tadaki Suzuki: National Institute of Infectious Diseases
Kenzo Tokunaga: National Institute of Infectious Diseases

Nature Communications, 2021, vol. 12, issue 1, 1-9

Abstract: Abstract The causative agent of the COVID-19 pandemic, SARS-CoV-2, is steadily mutating during continuous transmission among humans. Such mutations can occur in the spike (S) protein that binds to the ACE2 receptor and is cleaved by TMPRSS2. However, whether S mutations affect SARS-CoV-2 cell entry 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 that of SARS-CoV S. Among S variants, the D614G mutant shows the highest cell entry, as supported by structural and binding analyses. Nevertheless, the D614G mutation does not affect neutralization by antisera against prototypic viruses. Taken together, we conclude that the D614G mutation increases cell entry by acquiring higher affinity to ACE2 while maintaining neutralization susceptibility. Based on these findings, further worldwide surveillance is required to understand SARS-CoV-2 transmissibility among humans.

Date: 2021
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DOI: 10.1038/s41467-021-21118-2

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