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].

Abstract

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.

Supporting text Virus Host Location
Animals 1948 Antibodies, Monoclonal 26 Antibodies, Neutralizing 80 Cell Line 158 COVID-19 425 COVID-19 Serotherapy 8 HEK293 Cells 61 Humans 1440 Immunization, Passive 8 Mammals 92 Mice 253 Mutation 209 Pandemics 108 Primates 28 Protein Binding 193 SARS-CoV-2 453 Spike Glycoprotein, Coronavirus 274 Tropism 11 spike protein, SARS-CoV-2 157

Evidence records

3 total
Experimental Infection
1 records · 1 evidence types
Evidence type
1 records
OVE5235
Key finding

Pseudoviruses representing SARS-CoV-2 variants B.1.351, B.1.525, and B.1.526 showed increased infectivity in human and monkey cell lines, with enhanced entry observed in Calu-3 cells.

Virus
Host
Location
Not specified
Supporting text

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.

Method
pseudovirus infectivity assay | cell infection experiment
Experimental system
SARS-CoV-2 pseudovirus cell-culture infection assay
Functional Mechanism
2 records · 1 evidence types
Evidence type
2 records
OVE5233
Key finding

RBD mutations K417T/N, L452R, Y453F, S477N, E484K, and N501Y in SARS-CoV-2 spike confer immune escape from most tested monoclonal antibodies.

Virus
Host
Not specified
Location
Not specified
Supporting text

Emerging mutations in SARS-CoV-2 cause several waves of COVID-19 pandemic. RBD amino acid mutations comprising K417T/N, L452R, Y453F, S477N, E484K, and N501Y cause significant immune escape from 11 of 13 monoclonal antibodies.

Genes or proteins
spike | RBD
Host factors
monoclonal antibodies
Mutations
K417T | K417N | L452R | Y453F | S477N | E484K | N501Y
Mechanism types
immune escape
OVE5232
Key finding

Spike mutations K417N/T, N501Y, and E484K in SARS-CoV-2 variants increased infection of mouse ACE2-overexpressing cells, demonstrating host-range adaptation.

Virus
Host
Not specified
Location
Not specified
Supporting text

Emerging mutations in SARS-CoV-2 cause several waves of COVID-19 pandemic. The K417N/T, N501Y, or E484K-carrying variants exhibit significantly increased abilities to infect mouse ACE2-overexpressing cells.

Genes or proteins
spike | ACE2
Receptors
ACE2
Mutations
K417N | K417T | N501Y | E484K
Mechanism types
host-range expansion | receptor usage | host entry