OmniVira

Literature detail

Analysis of SARS-CoV-2 variant mutations reveals neutralization escape mechanisms and the ability to use ACE2 receptors from additional species.

Ruoke Wang1,2 Qi Zhang3 Jiwan Ge4 Wenlin Ren5,6 Rui Zhang3 Jun Lan4 Bin Ju7,8,9 Bin Su10 Fengting Yu11 Peng Chen3 Huiyu Liao10 Yingmei Feng10 Xuemei Li10 Xuanling Shi3 Zheng Zhang7,8,9 Fujie Zhang11 Qiang Ding5,6 Tong Zhang12 Xinquan Wang13 Linqi Zhang1,14,15
Affiliations 15 institutions
  1. NexVac Research Center, Comprehensive AIDS Research Center, Center for Infectious Disease Research, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing 100084, China
  2. Tsinghua-Peking Joint Center for Life Sciences, Beijing 100084, China.
  3. NexVac Research Center, Comprehensive AIDS Research Center, Center for Infectious Disease Research, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing 100084, China.
  4. The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  5. Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing 100084, China
  6. Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing 100084, China.
  7. Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital
  8. The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen 518112, Guangdong Province, China
  9. The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, China.
  10. Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.
  11. Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, No. 8, Jing Shun Dong Jie, Chaoyang, 100015 District Beijing, China.
  12. Beijing Youan Hospital, Capital Medical University, Beijing 100069, China. Electronic address: [email protected].
  13. The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: [email protected].
  14. Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China
  15. Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen 518132, China. Electronic address: [email protected].
PMID 34166623 2021 Immunity eng ppublish
PubMed DOI Browse context

Article

Publication summary

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge during the global pandemic and may facilitate escape from current antibody therapies and vaccine protection. Here we showed that the South African variant B.1.351 was the most resistant to current monoclonal antibodies and convalescent plasma from coronavirus disease 2019 (COVID-19)-infected individuals, followed by the Brazilian variant P.1 and the United Kingdom variant B.1.1.7. This resistance hierarchy corresponded with Y144del and 242-244del mutations in the N-terminal domain and K417N/T, E484K, and N501Y mutations in the receptor-binding domain (RBD) of SARS-CoV-2. Crystal structure analysis of the B.1.351 triple mutant (417N-484K-501Y) RBD complexed with the monoclonal antibody P2C-1F11 revealed the molecular basis for antibody neutralization and escape. B.1.351 and P.1 also acquired the ability to use mouse and mink ACE2 receptors for entry. Our results demonstrate major antigenic shifts and potential broadening of the host range for B.1.351 and P.1 variants, which poses serious challenges to current antibody therapies and vaccine protection.

antibody immune escape neutralization SARS-CoV-2 variant of concern Immune Evasion Angiotensin-Converting Enzyme 2 Animals Antibodies, Monoclonal Antibodies, Neutralizing Antigenic Variation COVID-19 Host Specificity Humans Mice Mink Mutation Protein Binding

Structured evidence records

Evidence records

6 total
Receptor Usage 4 records
Receptor Usage Extraction confidence 0.95
Key finding

The SARS-CoV-2 variant B.1.351 can use mouse ACE2 receptors for cell entry.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

B.1.351 and P.1 also acquired the ability to use mouse and mink ACE2 receptors for entry.

Receptors
ACE2
Receptor Usage Extraction confidence 0.95
Key finding

The SARS-CoV-2 variant B.1.351 can use mink ACE2 receptors for cell entry.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

B.1.351 and P.1 also acquired the ability to use mouse and mink ACE2 receptors for entry.

Receptors
ACE2
Receptor Usage Extraction confidence 0.95
Key finding

The SARS-CoV-2 variant P.1 can use mouse ACE2 receptors for cell entry.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

B.1.351 and P.1 also acquired the ability to use mouse and mink ACE2 receptors for entry.

Receptors
ACE2
Receptor Usage Extraction confidence 0.95
Key finding

The SARS-CoV-2 variant P.1 can use mink ACE2 receptors for cell entry.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

B.1.351 and P.1 also acquired the ability to use mouse and mink ACE2 receptors for entry.

Receptors
ACE2
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.85
Key finding

Genomic and structural analyses identified spike RBD mutations in SARS-CoV-2 variants B.1.351, P.1, and B.1.1.7 that underpin antibody escape and suggest evolutionary changes enabling broader host receptor use.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

The resistance hierarchy corresponded with Y144del and 242-244del mutations in the N-terminal domain and K417N/T, E484K, and N501Y mutations in the receptor-binding domain (RBD) of SARS-CoV-2. Crystal structure analysis of the B.1.351 triple mutant (417N-484K-501Y) RBD complexed with the monoclonal antibody P2C-1F11 revealed the molecular basis for antibody neutralization and escape.

Genes or proteins
Spike Glycoprotein; receptor-binding domain; ACE2
Analysis methods
mutation analysis; crystal structure analysis; comparative genomic analysis
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

SARS-CoV-2 variants B.1.351 and P.1 show spike mutations K417N/T, E484K, and N501Y that promote antibody escape and allow viral entry via mouse and mink ACE2 receptors.

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

B.1.351 and P.1 also acquired the ability to use mouse and mink ACE2 receptors for entry. This resistance hierarchy corresponded with Y144del and 242-244del mutations in the N-terminal domain and K417N/T, E484K, and N501Y mutations in the receptor-binding domain (RBD) of SARS-CoV-2.

Genes or proteins
Spike; receptor-binding domain; N-terminal domain
Receptors
ACE2
Mutations
Y144del; 242-244del; K417N/T; E484K; N501Y
Mechanism types
immune_escape; receptor_binding; host_range_expansion