The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity

By Qian-qian Li, Jia-jing Wu, J. Nie, Li Zhang, H. Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, L. Nie and 10 more. 2020

1,435 citations recorded by the source corpus.

The spike protein of SARS-CoV-2 has been undergoing mutations and is highly glycosylated. It is critically important to investigate the biological significance of these mutations. Here, we investigated 80 variants and 26 glycosylation site modifications for the infectivity and reactivity to a panel of neutralizing antibodies and sera from convalescent patients. D614G, along with several variants containing both D614G and another amino acid change, were significantly more infectious. Most variants with amino acid change at receptor binding domain were less infectious, but variants including A475V, L452R, V483A, and F490L became resistant to some neutralizing antibodies. Moreover, the majority of glycosylation deletions were less infectious, whereas deletion of both N331 and N343 glycosylation drastically reduced infectivity, revealing the importance of glycosylation for viral infectivity. Interestingly, N234Q was markedly resistant to neutralizing antibodies, whereas N165Q became more sensitive. These findings could be of value in the development of vaccine and therapeutic antibodies.

Subfields: Ecology, Infectious Diseases, Molecular Biology

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Citations in the corpus

Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology (2020, positive): “This is supported by the fact that naturally occurring RBD mutations were recently associated with escape from mAb binding and with reduced recognition by immune sera (Li et al., 2020b).”
SARS-CoV-2 D614G Variant Exhibits Efficient Replication ex vivo and Transmission in vivo (2020, neutral): “Using pseudotype viruses, the D614G substitution has been suggested to increase proteolytic cleavage and S glycoprotein incorporation into virions, reduce S1 loss and promote enhanced infectivity in vitro (4, 9, 21).”
COVID-19 and the human innate immune system (2021, background): “Although many mutations decreased infectivity, the virus variant D614G in the spike protein of SARS-CoV-2 increased infectivity (Li et al., 2020).”
Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization (2021, background): “The relatively low genetic barrier to resistance combined with knowledge of the presence of relevant substitutions in clinical isolates suggests that effective mAb therapy will likely require a combination of at least two neutralizing antibodies (ACTIV-3/ TICO LY-CoV555 Study Group, 2020; Baum et al”
Adaptive immunity to SARS-CoV-2 and COVID-19 (2021, background): “…accompanied by innate cell immunopathology and a plasma cytokine signature of elevated CXCL10, interleukin (IL)-6, and IL-8 in many studies (Aid et al., 2020; KuriCervantes et al., 2020; Li et al., 2020b; Lucas et al., 2020; Radermecker et al., 2020; Schurink et al., 2020; Del Valle et al., 2020).”