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<p>Mechanism and functional activity of V1WT_06, V1WT_41, and VA14_26.</p> Ayush Upadhyay (25157573) Jeffrey Seow (9415776) Yilmaz Alguel (24840073) Joseph Newman (5638340) Nazia Thakur (9904162) Abigail L. Hay (25157576) Jerry C. H. Tam (13955938) Andrea Nans (5176226) Richard J. Orton (7832015) Dalan Bailey (193037) Peter Cherepanov (369) Katie J. Doores (346210) Biophysics Microbiology Evolutionary Biology Ecology Immunology Biological Sciences not elsewhere classified Hematology Infectious Diseases Virology v1wt_06 contact residues therapeutic antibody development reactive monoclonal antibodies mab v1wt_06 binds increasing spillover potential human population presents heavy chain alone future therapeutic use confer broad sarbecovirus circulating viruses suggesting 2 variant neutralisation 2 variants xlink "> virus entry urgent need rationale design rational design neutralising epitopes including xec ideal candidates highly conserved functionally constrained discover cross differing angles continuing evolution ace2 competition <p>Neutralisation of sarbecoviruses through entry via different host ACE2s. Neutralisation of <b>A)</b> Rc-o319 and <b>B)</b> RhGB07 was measured against entry via <i>Rh. cornutus</i> ACE2 and <i>Rh. alcyone</i> ACE2, respectively, which were transiently expressed in HEK293T/17 cells. <b>C)</b> Neutralisation of WIV-1 was compared between entry via hu-ACE2 (dotted line and closed symbols) and <i>Rh. alcyone</i> ACE2 (full line and closed symbols). Neutralisation was measured using HEK 293T cells transiently expressing either <i>Human</i> ACE2 or <i>Rh. alcyone</i> ACE2. For A-C, mean values are plotted with error bars showing ± standard deviation (s.d.). <b>D)</b> Ability of IgGs to inhibit the interaction between cell surface ACE2 (including hu-ACE2, <i>Rh. cornutus</i> ACE2 and <i>Rh. alcyone</i> ACE2) and soluble RBD (including SARS-CoV-2, WIV-1, Rs4231, RhBG07, and Rc-o319 RBDs). IgGs were pre-incubated with fluorescently labelled RBD before addition to ACE2 expressing cells. N.B = No binding of IgG to the RBD. The percentage reduction in mean fluorescence intensity is reported. Experiments were performed in duplicate. <b>E)</b> Antibody dependant cellular cytotoxicity (ADCC) of IgGs measured through the surface expression of CD107a on activated NK cells (NK-92 cells expressing CD16) [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3003882#pbio.3003882.ref041" target="_blank">41</a>]. HIV-1 specific neutralising antibody, PGT128 is used as a negative control [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3003882#pbio.3003882.ref031" target="_blank">31</a>]. The data underlying this Figure can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3003882#pbio.3003882.s010" target="_blank">S1 Data</a>.</p> 2026-10-01T17:40:02Z Image Figure 10.1371/journal.pbio.3003882.g004 https://figshare.com/articles/figure/_p_Mechanism_and_functional_activity_of_V1WT_06_V1WT_41_and_VA14_26_p_/34048942 CC BY 4.0