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oai:figshare.com:article/34047364 2026-10-01T17:22:52Z category_8 category_12 category_24 category_272 category_39 category_46 category_734 category_64 category_132 category_134 portal_5 item_type_6 month_year_10_2026

<p>Uncropped western blot images in this study.</p> 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 <div><p>Sarbecoviruses interact with their receptor, angiotensin-converting enzyme 2 (ACE2), via the receptor-binding domain (RBD) of Spike, the immunodominant target for neutralising antibodies. Understanding the interplay and correlation between ACE2-determined host range and antigenicity is vitally important for understanding the zoonotic potential of related bat sarbecoviruses. Using binding assays, pseudotype-entry assays and a diverse panel of mammalian ACE2 proteins, we examined the host range and related antigenicity of multiple bat coronaviruses. Broad bat ACE2 usage (a <i>generalist</i> phenotype) was most common in clade 1 sarbecoviruses, including SARS-CoV-2 and the BANAL isolates from Laos. In contrast, clade 3 (e.g., RhGB07) and 5 (e.g., Rc-o319) sarbecoviruses exhibited more restricted ACE2 usage (a <i>specialist</i> phenotype). A novel structure for RhGB07 Spike further helped to identify RBD residues associated with this receptor specialism. Interestingly, the generalist phenotypes were largely maintained with more diverse mammalian receptor libraries, including human, non-human primate, livestock, rodent ACE2 and potential intermediate reservoir hosts (e.g., civet, racoon dog, pangolin), while specialists, like RhGB07, exhibited wider phenotypic diversity. The impact of SARS-CoV-2’s continued evolution in humans was also examined, identifying an expanding and/or shifting pattern of generalism for variants, especially Omicron and its sub-lineages. Furthermore, we compared and correlated these entry phenotypes with antigenicity using sera from SARS-CoV-2 convalescent individuals. Clade 1 viruses, phylogenetically related to SARS-CoV-2, were antigenically the most similar, with robust evidence for cross-neutralisation; however, there was still evidence for limited cross-neutralisation across the entire sub-genus. Finally, using monoclonal antibodies, derived from COVID-19 vaccinees with breakthrough infections, we pin-pointed the antibody epitope classes responsible for wider neutralisation. Our research indicates that generalist ACE2-using sarbecoviruses are phylogenetically and antigenically related to SARS-CoV-2.</p></div> 2026-10-01T17:40:07Z Text Journal contribution 10.1371/journal.pbio.3003944.s018 https://figshare.com/articles/journal_contribution/_p_Uncropped_western_blot_images_in_this_study_p_/34047364 CC BY 4.0