Literature detail

SARS-CoV-2 501Y.V2 variants lack higher infectivity but do have immune escape.

Qianqian Li1 Jianhui Nie1 Jiajing Wu1 Li Zhang1 Ruxia Ding1 Haixin Wang1 Yue Zhang1 Tao Li1 Shuo Liu1 Mengyi Zhang1 Chenyan Zhao1 Huan Liu1 Lingling Nie1 Haiyang Qin1 Meng Wang1 Qiong Lu1 Xiaoyu Li1 Junkai Liu1 Haoyu Liang1 Yi Shi2 Yuelei Shen3 Liangzhi Xie4 Linqi Zhang5 Xiaowang Qu6 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, No. 31 Huatuo Street, Daxing District, Beijing 102629, China.
  2. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.
  3. Beijing Biocytogen Co., Ltd., Beijing 101111, China.
  4. Beijing Antibody Research Key Laboratory, Sino Biological Inc., Building 9, Jing Dong Bei Technology Park, No. 18 Ke Chuang 10th St., BDA, Beijing 100176, China.
  5. Center for Global Health and Infectious Diseases, Comprehensive AIDS Research Center, and Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing 100084, China.
  6. Translational Medicine Institute, The First People's Hospital of Chenzhou, University of South China, Chenzhou 423000, China. Electronic address: [email protected].
  7. National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address: [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, No. 31 Huatuo Street, Daxing District, Beijing 102629, China. Electronic address: [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, No. 31 Huatuo Street, Daxing District, Beijing 102629, China. Electronic address: [email protected].
PMID 33735608 2021 Cell eng ppublish
PubMed DOI Browse context

Article

Publication summary

The 501Y.V2 variants of SARS-CoV-2 containing multiple mutations in spike are now dominant in South Africa and are rapidly spreading to other countries. Here, experiments with 18 pseudotyped viruses showed that the 501Y.V2 variants do not confer increased infectivity in multiple cell types except for murine ACE2-overexpressing cells, where a substantial increase in infectivity was observed. Notably, the susceptibility of the 501Y.V2 variants to 12 of 17 neutralizing monoclonal antibodies was substantially diminished, and the neutralization ability of the sera from convalescent patients and immunized mice was also reduced for these variants. The neutralization resistance was mainly caused by E484K and N501Y mutations in the receptor-binding domain of spike. The enhanced infectivity in murine ACE2-overexpressing cells suggests the possibility of spillover of the 501Y.V2 variants to mice. Moreover, the neutralization resistance we detected for the 501Y.V2 variants suggests the potential for compromised efficacy of monoclonal antibodies and vaccines.

501Y.V2 E484K immune escape infectivity K417N mutation N501Y neutralizing antibody receptor binding region SARS-CoV-2 Immune Evasion Angiotensin-Converting Enzyme 2 Antibodies, Monoclonal Antibodies, Neutralizing Antigens, Viral Cell Line, Tumor COVID-19 HEK293 Cells

Structured evidence records

Evidence records

3 total
1 records
Extraction confidence 0.90
Key finding

Pseudotyped SARS-CoV-2 501Y.V2 variants exhibited substantially increased infectivity in murine ACE2-overexpressing cells, suggesting possible adaptation to mouse ACE2.

Virus
Location
Not specified
Supporting text

Experiments with 18 pseudotyped viruses showed that the 501Y.V2 variants do not confer increased infectivity in multiple cell types except for murine ACE2-overexpressing cells, where a substantial increase in infectivity was observed.

Method
pseudovirus infection; infectivity assay
Experimental system
pseudovirus assay
1 records
Extraction confidence 0.95
Key finding

SARS-CoV-2 501Y.V2 variants carrying E484K and N501Y mutations in spike show immune escape and increased infectivity in murine ACE2-overexpressing cells.

Virus
Host
Not specified
Location
Not specified
Supporting text

The neutralization resistance was mainly caused by E484K and N501Y mutations in the receptor-binding domain of spike. The enhanced infectivity in murine ACE2-overexpressing cells suggests the possibility of spillover of the 501Y.V2 variants to mice.

Genes or proteins
spike
Receptors
ACE2
Mutations
E484K; N501Y
Mechanism types
immune_escape; receptor_binding; host_factor_interaction
1 records
Extraction confidence 0.85
Key finding

SARS-CoV-2 501Y.V2 variants containing N501Y and E484K mutations in the receptor-binding domain showed enhanced infectivity in murine ACE2-overexpressing cells, indicating altered ACE2 receptor usage.

Virus
Location
Not specified
Supporting text

The 501Y.V2 variants do not confer increased infectivity in multiple cell types except for murine ACE2-overexpressing cells, where a substantial increase in infectivity was observed. The neutralization resistance was mainly caused by E484K and N501Y mutations in the receptor-binding domain of spike.

Method
pseudotyped virus infectivity assay
Receptors
ACE2