Scientists computationally restore the potency of an antibody against SARS-CoV-2 Omicron subvariants Antibody Omicron SARSCoV2 Coronavirus Disease COVID biorxivpreprint Livermore_Lab VUMC_Vaccines WUSTLmed LosAlamosNatLab
By Dr. Chinta SidharthanOct 27 2022Reviewed by Danielle Ellis, B.Sc. In a recent study posted to the bioRxiv* preprint server, a team of researchers from the United States computationally modified the COV2-2130 monoclonal antibody to restore its neutralizing ability against the severe acute respiratory syndrome coronavirus 2 Omicron subvariants, while retaining efficacy against the Delta and wild-type strains.
A combination of tixagevimab and cilgavimab was used as a prophylactic antibody therapy and had potent neutralizing effects on the ancestral Wuhan-1 strain and earlier variants of SARS-CoV-2 such as delta, was ineffective against the Omicron subvariants BA.1 and BA.1.1. The computational platform introduced mutations to COV2-2130 to propose antibody candidates. This method does not use inputs from wet lab experiments on the candidate antibodies or any derivatives of the original COV2-2130 antibody. The team used the RBDs of SARS-CoV-2 Delta variant, and Omicron subvariants BA.1 and BA1.1 as target antigens. Mutations were introduced to 20 paratope residues, especially in the heavy and light chains complementarity determining regions of the antibody.
The performance of the manufactured antibodies was tested using neutralization assays against pseudoviruses. Focus reduction neutralization test using several SARS-CoV-2 strains and Vero cells expressing transmembrane serine protease 2 was performed to determine the authentic neutralization activity against the virus.
When K18-hACE2 transgenic mice intranasally inoculated with the wild-type, or Omicron BA.1.1 or BA.5 variants were administered 2130-1-0114-112 and the original COV2-2130, 2130-1-0114-112 exhibited higher in vivo antiviral activity. Lab Diagnostics & Automation eBook Compilation of the top interviews, articles, and news in the last year. Download a copy today Cryo-EM structure of neutralizing antibodies 2130-1-0114-112 in complex with Cov2 BA.2 RBD. Cryo-EM map and model of the RBD-Fab complex. The map is transparent and colored by chain with RBD red, 2130-1-0114-112 HC yellow and 2130-1-0114-112 LC green. Atomic model of the RBD-Fab complex. Color as in A. Hydrogen bond in dashed line. BA.2 RBD mutation in orange.
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