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

ABSTRACT: 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.

SUBMITTER: Li Q

PROVIDER: S-EPMC7366990 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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

Li Qianqian Q Wu Jiajing J Nie Jianhui J Zhang Li L Hao Huan H Liu Shuo S Zhao Chenyan C Zhang Qi Q Liu Huan H Nie Lingling L Qin Haiyang H Wang Meng M Lu Qiong Q Li Xiaoyu X Sun Qiyu Q Liu Junkai J Zhang Linqi L Li Xuguang X Huang Weijin W Wang Youchun Y

Cell 20200717 5

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 variant ...[more]

PMID: 32730807

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Project description:SARS‐CoV‐2 has become an increasingly dangerous virus infecting 77.6 million people and resulting in over 2 million deaths in the last year. The spike glycoprotein plays an important role in the viral infection process by recognizing and binding to the ACE2 receptor in host's cells. Due to the importance of this protein, current research efforts are focused on mutations that impact viral infectivity. SARS‐CoV‐2 viruses with a spike mutation at position 614 were recently shown to be more infectious than their wild‐type ancestor. The D614G substitution eliminates a hydrogen bond with a threonine residue (T859) in an adjacent protein chain, allowing the spike protein to assume more readily an open conformation. Since the open conformation mediates attachment to the ACE2 receptor, the D614G mutant causes higher infectivity than the wild‐type spike protein. The main goal of this research was to create physical 3D printed models of the wild‐type and mutant spike proteins to visualize the molecular changes caused by the D614G mutation. Structural analyses of the wild‐type and the D614G spike mutant were performed using the Protein Data Bank files, 6vxx and 6xs6. To visualize the conformational changes caused by the D614G mutation, the protein structure alignments were performed using Pymol. A combined file containing the superimposed structures was imported into Jmol to create the scripts for model construction and 3D printing. A small protein model was built to describe the overall structure of the spike and the location of the amino acids linked to higher viral infectivity. An additional detailed model was constructed to illustrate the biochemical interactions at the mutation site. In this model, important amino acids such as Asp614, Ala647, and Thr859 are highlighted due to their role in hydrogen bonding and spike protein binding to the ACE2 receptor. A magnetic piece was created to show the effects of the aspartic acid to glycine mutation at position 614. A Jmol tutorial was designed to complement the 3D models and assess students’ learning of the structure and function of SARS‐CoV‐2 spike protein. This exercise will allow undergraduate students and faculty to visualize and better understand how single amino acid mutations can lead to changes in viral infectivity.

Dataset Information

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

Publications

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

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