OmniVira

Literature detail

Ten emerging SARS-CoV-2 spike variants exhibit variable infectivity, animal tropism, and antibody neutralization.

Li Zhang1 Zhimin Cui1 Qianqian Li1,2 Bo Wang3,4 Yuanling Yu1 Jiajing Wu1 Jianhui Nie1 Ruxia Ding1 Haixin Wang1 Yue Zhang1 Shuo Liu1 Zhihai Chen5 Yaqing He6 Xiaodong Su3,4 Wenbo Xu7 Weijin Huang8 Youchun Wang9
Affiliations 9 institutions
  1. Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC) and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, China.
  2. Jiangsu Recbio Technology Co., Ltd., Taizhou, China.
  3. Beijing Advanced Innovation Center for Genomics (ICG) & Biomedical Pioneering Innovation Center (BIOPIC), Peking University
  4. State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.
  5. Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
  6. Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China.
  7. National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. [email protected].
  8. Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC) and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, China. [email protected].
  9. Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC) and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, China. [email protected].
PMID 34645933 2021 Commun Biol eng epublish
PubMed DOI Browse context

Article

Publication summary

Emerging mutations in SARS-CoV-2 cause several waves of COVID-19 pandemic. Here we investigate the infectivity and antigenicity of ten emerging SARS-CoV-2 variants-B.1.1.298, B.1.1.7(Alpha), B.1.351(Beta), P.1(Gamma), P.2(Zeta), B.1.429(Epsilon), B.1.525(Eta), B.1.526-1(Iota), B.1.526-2(Iota), B.1.1.318-and seven corresponding single amino acid mutations in the receptor-binding domain using SARS-CoV-2 pseudovirus. The results indicate that the pseudovirus of most of the SARS-CoV-2 variants (except B.1.1.298) display slightly increased infectivity in human and monkey cell lines, especially B.1.351, B.1.525 and B.1.526 in Calu-3 cells. The K417N/T, N501Y, or E484K-carrying variants exhibit significantly increased abilities to infect mouse ACE2-overexpressing cells. The activities of furin, TMPRSS2, and cathepsin L are increased against most of the variants. RBD amino acid mutations comprising K417T/N, L452R, Y453F, S477N, E484K, and N501Y cause significant immune escape from 11 of 13 monoclonal antibodies. However, the resistance to neutralization by convalescent serum or vaccines elicited serum is mainly caused by the E484K mutation. The convalescent serum from B.1.1.7- and B.1.351-infected patients neutralized the variants themselves better than other SARS-CoV-2 variants. Our study provides insights regarding therapeutic antibodies and vaccines, and highlights the importance of E484K mutation.

Animals Antibodies, Monoclonal Antibodies, Neutralizing Cell Line COVID-19 COVID-19 Serotherapy HEK293 Cells Humans Immunization, Passive Mammals Mice Mutation Pandemics Primates Protein Binding SARS-CoV-2 Spike Glycoprotein, Coronavirus Tropism

Structured evidence records

Evidence records

5 total
Receptor Usage 2 records
Receptor Usage Extraction confidence 0.90
Key finding

SARS-CoV-2 spike variants with K417N/T, N501Y, or E484K mutations show increased infection of cells expressing mouse ACE2, suggesting mutation-dependent receptor compatibility changes.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

The K417N/T, N501Y, or E484K-carrying variants exhibit significantly increased abilities to infect mouse ACE2-overexpressing cells.

Method
pseudovirus assay
Receptors
ACE2
Receptor Usage Extraction confidence 0.90
Key finding

Furin, TMPRSS2, and cathepsin L demonstrate elevated activity toward most SARS-CoV-2 variants, indicating altered host factor interactions involved in viral entry.

Virus
SARS-CoV-2
Host
Not specified
Location
Not specified
Supporting text

The activities of furin, TMPRSS2, and cathepsin L are increased against most of the variants.

Host factors
furin; TMPRSS2; cathepsin L
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.75
Key finding

Distinct SARS-CoV-2 spike mutations such as K417N/T, E484K, and N501Y define multiple variants with altered host tropism and antibody neutralization capacity, indicating ongoing genomic evolution across lineages.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

The abstract specifies ten emerging SARS-CoV-2 variants (B.1.1.298, B.1.1.7, B.1.351, P.1, P.2, B.1.429, B.1.525, B.1.526, B.1.1.318) and corresponding RBD mutations (K417T/N, L452R, Y453F, S477N, E484K, N501Y), indicating that these spike amino acid substitutions lead to variable infectivity and immune escape.

Genes or proteins
Spike; Receptor-binding domain
Analysis methods
comparative genomic analysis of spike mutations
Host Range Experiment 1 records
Host Range Experiment Extraction confidence 0.95
Key finding

SARS-CoV-2 pseudoviruses of variants containing K417N/T, N501Y, or E484K mutations showed increased infection efficiencies in mouse ACE2-expressing cells, while several variants exhibited heightened infectivity in human and monkey cell lines.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

The pseudovirus of most of the SARS-CoV-2 variants (except B.1.1.298) display slightly increased infectivity in human and monkey cell lines, especially B.1.351, B.1.525 and B.1.526 in Calu-3 cells. The K417N/T, N501Y, or E484K-carrying variants exhibit significantly increased abilities to infect mouse ACE2-overexpressing cells.

Method
cell-entry assay; pseudovirus assay
Experimental system
pseudovirus assay
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

Several SARS-CoV-2 spike RBD mutations, particularly E484K, K417N/T, and N501Y, enhance cross-species receptor usage and immune escape, supporting molecular adaptation of the virus.

Virus
SARS-CoV-2
Host
Not specified
Location
Not specified
Supporting text

The K417N/T, N501Y, or E484K-carrying variants exhibit significantly increased abilities to infect mouse ACE2-overexpressing cells. RBD amino acid mutations comprising K417T/N, L452R, Y453F, S477N, E484K, and N501Y cause significant immune escape from 11 of 13 monoclonal antibodies. However, the resistance to neutralization by convalescent serum or vaccines elicited serum is mainly caused by the E484K mutation.

Genes or proteins
spike; receptor-binding domain
Receptors
ACE2
Host factors
furin; TMPRSS2; cathepsin L
Mutations
K417N; K417T; L452R; Y453F; S477N; E484K; N501Y
Mechanism types
receptor_binding; cell_entry; immune_escape; tropism; pathogenicity