SARS-CoV-2 escape from a highly neutralizing COVID-19 convalescent plasma.
Amino Acid Substitution
Angiotensin-Converting Enzyme 2
/ chemistry
Animals
Antibodies, Neutralizing
/ chemistry
Antibodies, Viral
/ chemistry
Binding Sites
COVID-19
/ genetics
Chlorocebus aethiops
Convalescence
Gene Expression
Humans
Immune Evasion
Immune Sera
/ chemistry
Models, Molecular
Mutation
Neutralization Tests
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
SARS-CoV-2
/ drug effects
Spike Glycoprotein, Coronavirus
/ chemistry
Vero Cells
COVID-19
SARS-CoV-2
antibody response
emerging variants
immune evasion
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
07 09 2021
07 09 2021
Historique:
entrez:
21
8
2021
pubmed:
22
8
2021
medline:
1
9
2021
Statut:
ppublish
Résumé
To investigate the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the immune population, we coincupi bated the authentic virus with a highly neutralizing plasma from a COVID-19 convalescent patient. The plasma fully neutralized the virus for seven passages, but, after 45 d, the deletion of F140 in the spike N-terminal domain (NTD) N3 loop led to partial breakthrough. At day 73, an E484K substitution in the receptor-binding domain (RBD) occurred, followed, at day 80, by an insertion in the NTD N5 loop containing a new glycan sequon, which generated a variant completely resistant to plasma neutralization. Computational modeling predicts that the deletion and insertion in loops N3 and N5 prevent binding of neutralizing antibodies. The recent emergence in the United Kingdom, South Africa, Brazil, and Japan of natural variants with similar changes suggests that SARS-CoV-2 has the potential to escape an effective immune response and that vaccines and antibodies able to control emerging variants should be developed.
Identifiants
pubmed: 34417349
pii: 2103154118
doi: 10.1073/pnas.2103154118
pmc: PMC8433494
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Immune Sera
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI127521
Pays : United States
Organisme : NIH HHS
ID : GM132826
Pays : United States
Organisme : NIH HHS
ID : R01 AI12751
Pays : United States
Organisme : European Research Council
Pays : International
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2021 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
Competing interest statement: R.R. is an employee of the GSK group of companies. E.A., I.P., E.P., N.M., and R.R. are listed as inventors of full-length human monoclonal antibodies described in Italian patent applications 102020000015754 filed on June 30, 2020 and 102020000018955 filed on August 3, 2020.
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