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oai:figshare.com:article/34047346 2026-10-01T17:22:44Z category_8 category_12 category_24 category_272 category_39 category_46 category_734 category_64 category_132 category_134 portal_5 item_type_1 month_year_10_2026

Binding of sarbceovirus RBDs with monoclonal antibodies isolated from SARS-CoV-2 breakthrough infections. Nazia Thakur (9904162) Joseph Newman (5638340) Dongchun Ni (15188356) Jeffrey Seow (9415776) Abigail L. Hay (25157576) Yeonjae Lee (12256119) Ayush Upadhyay (25157573) Babatunde E. Ekundayo (25157578) John A. Hammond (7431785) Thomas P. Peacock (6536120) Kelvin Lau (1847764) Katie J. Doores (346210) Dalan Bailey (193037) Microbiology Cell Biology Evolutionary Biology Environmental Sciences not elsewhere classified Ecology Immunology Biological Sciences not elsewhere classified Cancer Infectious Diseases Virology multiple bat coronaviruses g ., rc g ., civet clade 1 viruses restricted ace2 usage mammalian ace2 proteins g ., rhgb07 using monoclonal antibodies clade 1 sarbecoviruses div >< p determined host range converting enzyme 2 2 convalescent individuals ace2 ), via using binding assays antigenicity using sera related bat sarbecoviruses using sarbecoviruses host range clade 3 pangolin ), neutralising antibodies entry assays binding domain sarbecoviruses interact sarbecoviruses exhibited rodent ace2 like rhgb07 generalist ace2 related antigenicity zoonotic potential vitally important still evidence specialist </ shifting pattern robust evidence research indicates racoon dog novel structure largely maintained including human immunodominant target human primate generalist phenotypes generalist </ especially omicron entry phenotypes diverse panel continued evolution breakthrough infections The (A) WIV-1-RBD (blue)/ VA14_26 complex (green) (WIV-1 PDB 8WLZ [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3003944#pbio.3003944.ref049" target="_blank">49</a>]) is shown in cartoon representation. Only the VH and VL domains of the Fab of VA14_26 are shown for clarity. Residues of interest on the WIV-1 RBD that make contacts with VA14_26, R396, K366, A372 are coloured in orange. Contact residues on VA14_26 are coloured in purple. The inset shows a zoomed in highlight of this interface. A surface representation of VA14_26 coloured by electrostatic potential highlights that the WIV-1 RBD residues R396 and K366 that are positively charged bind and localise in a highly negative patch of the Fab demonstrating that VA14_26 interactions are mediated by charge attraction. (B) The WIV-1 RBD, along with Rc-o319 (PDB 9W78), SARS-CoV-2 (PDB 7DF3) and RhGB07 (PDB 9RDT), are rendered as cartoon representation or surfaces with electrostatic potential colouring. The residues of interest on the RBD are highlighted on the cartoon representation or of the surface. A critical interacting residue of the VA14_26, E106, is highlighted. This residue is attracted to the positively charged surface of the WIV-1 RBD. Homologous residues present in other RBD, decrease (Rco319) or reverse (RhGB07) this positive charge surface that decreases affinity of the VA14_26 antibody for these RBDs. (C) Each plot shows a single mAb binding, coloured by its designated antibody competition group (Group 1 = purple, Group 2 = orange, Group 3 = red, Group 3.5 = blue, Group 4 = green, Group 8 = non-RBD, NTD-specific) in an ELISA using purified RacCS203 RBD. The curves were calculated using a least-squares regression non-linear fit. Binding (EC50, µg/ml) titres are shown for each mAb against RacCS203, with limits of detection indicated (lower limit: <0.08g/ml upper limit: 5 µg/ml). Red boxes indicate mAbs that exhibit high binding with all sarbecoviruses tested. (C) Representative SPR kinetics binding curves showing the association and dissociation of mAb VA14_26 with bat sarbecovirus RBDs. Each line represents a RBD concentration, starting at 5 µg/ml and titrated 2-fold (8 dilutions). Calculated KD values are also shown. The data underlying this Figure can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3003944#pbio.3003944.s017" target="_blank">S1 Data</a>. (TIF) 2026-10-01T17:40:07Z Image Figure 10.1371/journal.pbio.3003944.s012 https://figshare.com/articles/figure/_p_Binding_of_sarbceovirus_RBDs_with_monoclonal_antibodies_isolated_from_SARS-CoV-2_breakthrough_infections_p_/34047346 CC BY 4.0