Contribution of single mutations to selected SARS-CoV-2 emerging variants spike antigenicity

被引:58
作者
Gong, Shang Yu [1 ,2 ]
Chatterjee, Debashree [1 ]
Richard, Jonathan [1 ,3 ]
Prevost, Jeremie [1 ,3 ]
Tauzin, Alexandra [1 ,3 ]
Gasser, Romain [1 ,3 ]
Bo, Yuxia [4 ,5 ]
Vezina, Dani [1 ,3 ]
Goyette, Guillaume [1 ]
Gendron-Lepage, Gabrielle [1 ]
Medjahed, Halima [1 ]
Roger, Michel [1 ,3 ]
Cote, Marceline [4 ,5 ,6 ]
Finzi, Andres [1 ,2 ,3 ]
机构
[1] CHUM, Ctr Rech, Montreal, PQ H2X 0A9, Canada
[2] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 0G4, Canada
[3] Univ Montreal, Dept Microbiol Infectiol & Immunol, Montreal, PQ H2X 0A9, Canada
[4] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON K1H 8M5, Canada
[5] Univ Ottawa, Ctr Infect Immun & Inflammat, Ottawa, ON K1H 8M5, Canada
[6] Inst Natl Sante Publ Quebec, Lab Sante Publ Quebec, Ste Anne De Bellevue, PQ H9X 3R5, Canada
基金
加拿大创新基金会;
关键词
Coronavirus; COVID-19; SARS-CoV-2; Spike glycoproteins; RBD; ACE2; Temperature; Variants of concern; Vaccines; ACE2;
D O I
10.1016/j.virol.2021.09.001
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Towards the end of 2020, multiple variants of concern (VOCs) and variants of interest (VOIs) have arisen from the original SARS-CoV-2 Wuhan-Hu-1 strain. Mutations in the Spike protein are highly scrutinized for their impact on transmissibility, pathogenesis and vaccine efficacy. Here, we contribute to the growing body of literature on emerging variants by evaluating the impact of single mutations on the overall antigenicity of selected variants and their binding to the ACE2 receptor. We observe a differential contribution of single mutants to the global variants phenotype related to ACE2 interaction and antigenicity. Using biolayer interferometry, we observe that enhanced ACE2 interaction is mostly modulated by a decrease in off-rate. Finally, we made the interesting observation that the Spikes from tested emerging variants bind better to ACE2 at 37 degrees C compared to the D614G variant. Whether improved ACE2 binding at higher temperature facilitates emerging variants transmission remain to be demonstrated.
引用
收藏
页码:134 / 145
页数:12
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