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TitleBroadly potent spike-specific human monoclonal antibodies inhibit SARS-CoV-2 Omicron sub-lineages.
Journal, issue, pagesCommun Biol, Vol. 7, Issue 1, Page 1239, Year 2024
Publish dateOct 2, 2024
AuthorsMelanie R Walker / Alexander Underwood / Kasper H Björnsson / Sai Sundar Rajan Raghavan / Maria R Bassi / Alekxander Binderup / Long V Pham / Santseharay Ramirez / Mette Pinholt / Robert Dagil / Anne S Knudsen / Manja Idorn / Max Soegaard / Kaituo Wang / Andrew B Ward / Ali Salanti / Jens Bukh / Lea Barfod /
PubMed AbstractThe continuous emergence of SARS-CoV-2 variants of concern has rendered many therapeutic monoclonal antibodies (mAbs) ineffective. To date, there are no clinically authorized therapeutic antibodies ...The continuous emergence of SARS-CoV-2 variants of concern has rendered many therapeutic monoclonal antibodies (mAbs) ineffective. To date, there are no clinically authorized therapeutic antibodies effective against the recently circulating Omicron sub-lineages BA.2.86 and JN.1. Here, we report the isolation of broad and potent neutralizing human mAbs (HuMabs) from a healthcare worker infected with SARS-CoV-2 early in the pandemic. These include a genetically unique HuMab, named K501SP6, which can neutralize different Omicron sub-lineages, including BQ.1, XBB.1, BA.2.86 and JN.1, by targeting a highly conserved epitope on the N terminal domain, as well as an RBD-specific HuMab (K501SP3) with high potency towards earlier circulating variants that was escaped by the more recent Omicron sub-lineages through spike F486 and E484 substitutions. Characterizing SARS-CoV-2 spike-specific HuMabs, including broadly reactive non-RBD-specific HuMabs, can give insight into the immune mechanisms involved in neutralization and immune evasion, which can be a valuable addition to already existing SARS-CoV-2 therapies.
External linksCommun Biol / PubMed:39354108 / PubMed Central
MethodsEM (single particle)
Resolution2.84 - 3.7 Å
Structure data

16441

8c5r

EMDB-16441, PDB-8c5r:
Omicron B.1.1.529 2 RBD up conformation
Method: EM (single particle) / Resolution: 3.7 Å

50503

9fjk

EMDB-50503, PDB-9fjk:
Omicron BA.1 Spike protein with neutralizing NTD specific mAb K501SP6
Method: EM (single particle) / Resolution: 2.84 Å

Source
  • alphacoronavirus
  • homo sapiens (human)
  • severe acute respiratory syndrome coronavirus 2
  • enterobacteria phage t4 (virus)
KeywordsVIRAL PROTEIN / COVID-19 / SPIKE TRIMER / OMICRON / B.1.1.529 / Neutralizing Antibody / Conserved Epitope / Spike

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