OmniVira

Literature detail

Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity.

Sophie M-C Gobeil1 Katarzyna Janowska1 Shana McDowell1 Katayoun Mansouri1 Robert Parks1 Victoria Stalls1 Megan F Kopp1 Kartik Manne1 Dapeng Li1 Kevin Wiehe1,2 Kevin O Saunders1,3,4,5 Robert J Edwards1,2 Bette Korber6 Barton F Haynes1,2,5 Rory Henderson7,2 Priyamvada Acharya7,3,8
Affiliations 8 institutions
  1. Duke Human Vaccine Institute, Durham, NC 27710, USA.
  2. Department of Medicine, Duke University, Durham, NC 27710, USA.
  3. Department of Surgery, Duke University, Durham, NC 27710, USA.
  4. Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA.
  5. Department of Immunology, Duke University, Durham, NC 27710, USA.
  6. Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
  7. Duke Human Vaccine Institute, Durham, NC 27710, USA. [email protected] [email protected].
  8. Department of Biochemistry, Duke University, Durham, NC 27710, USA.
PMID 34168071 2021 Science eng ppublish
PubMed DOI Browse context

Article

Publication summary

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with multiple spike mutations enable increased transmission and antibody resistance. We combined cryo-electron microscopy (cryo-EM), binding, and computational analyses to study variant spikes, including one that was involved in transmission between minks and humans, and others that originated and spread in human populations. All variants showed increased angiotensin-converting enzyme 2 (ACE2) receptor binding and increased propensity for receptor binding domain (RBD)-up states. While adaptation to mink resulted in spike destabilization, the B.1.1.7 (UK) spike balanced stabilizing and destabilizing mutations. A local destabilizing effect of the RBD E484K mutation was implicated in resistance of the B.1.1.28/P.1 (Brazil) and B.1.351 (South Africa) variants to neutralizing antibodies. Our studies revealed allosteric effects of mutations and mechanistic differences that drive either interspecies transmission or escape from antibody neutralization.

Amino Acid Substitution Angiotensin-Converting Enzyme 2 Animals Antibodies, Neutralizing Antibodies, Viral Antigens, Viral COVID-19 Cryoelectron Microscopy Host Adaptation Humans Immune Evasion Mink Models, Molecular Mutation Protein Binding Protein Conformation Protein Interaction Domains and Motifs Protein Structure, Quaternary

Structured evidence records

Evidence records

6 total
Genomic Evolution 2 records
Genomic Evolution Extraction confidence 0.90
Key finding

Genomic and structural analyses of SARS-CoV-2 spike variants revealed mutation-driven differences associated with adaptation in mink and human hosts.

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

We combined cryo-electron microscopy (cryo-EM), binding, and computational analyses to study variant spikes, including one that was involved in transmission between minks and humans, and others that originated and spread in human populations.

Genes or proteins
Spike Glycoprotein
Analysis methods
computational analysis
Genomic Evolution Extraction confidence 0.90
Key finding

The E484K mutation in the receptor-binding domain was identified as a genomic change contributing to antigenic evolution in SARS-CoV-2 variants from Brazil and South Africa.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

A local destabilizing effect of the RBD E484K mutation was implicated in resistance of the B.1.1.28/P.1 (Brazil) and B.1.351 (South Africa) variants to neutralizing antibodies.

Genes or proteins
Spike Glycoprotein; RBD
Analysis methods
computational analysis
Spillover Event 2 records
Spillover Event Extraction confidence 0.85
Key finding

A SARS-CoV-2 variant was implicated in transmission between minks and humans, indicating documented interspecies spillover.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

We combined cryo-electron microscopy (cryo-EM), binding, and computational analyses to study variant spikes, including one that was involved in transmission between minks and humans.

Method
cryo-electron microscopy; binding analysis; computational analysis
Transmission direction
animal-to-human
Spillover Event Extraction confidence 0.85
Key finding

Transmission of SARS-CoV-2 between humans and minks also implies human-to-animal spillback.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

We combined cryo-electron microscopy (cryo-EM), binding, and computational analyses to study variant spikes, including one that was involved in transmission between minks and humans.

Method
cryo-electron microscopy; binding analysis; computational analysis
Transmission direction
human-to-animal
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

SARS-CoV-2 spike mutations increased ACE2 receptor binding and antibody escape, with mink adaptation causing spike destabilization and the E484K mutation conferring resistance to neutralizing antibodies.

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

All variants showed increased angiotensin-converting enzyme 2 (ACE2) receptor binding and increased propensity for receptor binding domain (RBD)-up states. While adaptation to mink resulted in spike destabilization, the B.1.1.7 (UK) spike balanced stabilizing and destabilizing mutations. A local destabilizing effect of the RBD E484K mutation was implicated in resistance of the B.1.1.28/P.1 (Brazil) and B.1.351 (South Africa) variants to neutralizing antibodies.

Genes or proteins
spike; receptor binding domain
Receptors
ACE2
Mutations
E484K
Mechanism types
receptor_binding; immune_escape; host_adaptation; spike_stability
Receptor Usage 1 records
Receptor Usage Extraction confidence 0.90
Key finding

SARS-CoV-2 spike variants exhibit increased ACE2 receptor binding and altered RBD conformational states compared to reference strains.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

All variants showed increased angiotensin-converting enzyme 2 (ACE2) receptor binding and increased propensity for receptor binding domain (RBD)-up states.

Method
cryo-electron microscopy; binding assay; computational analysis
Receptors
ACE2