Together with HCoV-HKU1 and HCoV-OC43, these viruses belong to the β- coronavirus genus ( 4, 5). Among the seven HCoVs, SARS-CoV-2 closely resembles SARS-CoV-1 and, to a lesser degree, MERS-CoV. These include four endemic human CoVs (HCoVs) (HCoV-229E, HCoV-HKU1, HCoV-OC43, and HCoV-NL63) responsible for nonsevere, seasonal infections ( 4) as well as SARS-CoV-1 and MERS-CoV (Middle East respiratory syndrome CoV) that are associated with high morbidity and mortality in humans ( 6, 7). SARS-CoV-2 is a virus that belongs to the Coronaviridae family, of which six members have previously crossed into humans from animal reservoirs and established widespread infections ( 4, 5). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the current global pandemic ( 1– 3). Overall, our study describes a target on β-CoV spike proteins for protective antibodies that may facilitate the development of pan–β-CoV vaccines. Furthermore, we noted that CC40.8-like bnAbs are relatively rare in human COVID-19 infection, and therefore, their elicitation may require rational structure-based vaccine design strategies. In both models, CC40.8-treated animals exhibited less weight loss and reduced lung viral titers compared to controls. CC40.8 exhibited in vivo protective efficacy against SARS-CoV-2 challenge in two animal models. Conserved residues in β-CoVs interacted with CC40.8 antibody, thereby providing a molecular basis for its broad reactivity. We determined a crystal structure of CC40.8 Fab with a SARS-CoV-2 S2 stem peptide at 1.6-Å resolution and found that the peptide adopted a mainly helical structure.
Here, we showed that CC40.8 targets the conserved S2 stem helix region of the CoV spike fusion machinery.
We recently described a bnAb, CC40.8, from a CoV disease 2019 (COVID-19) convalescent donor that exhibits broad reactivity with human β-CoVs. Burton, and Raiees Andrabi Show Fewerīroadly neutralizing antibodies (bnAbs) to coronaviruses (CoVs) are valuable in their own right as prophylactic and therapeutic reagents to treat diverse CoVs and as templates for rational pan-CoV vaccine design. Panpan Zhou, Meng Yuan, Ge Song, Nathan Beutler, Namir Shaabani, Deli Huang, Wan-ting He, … Show All …, Xueyong Zhu, Sean Callaghan, Peter Yong, Fabio Anzanello, Linghang Peng, James Ricketts, Mara Parren, Elijah Garcia, Stephen A.
0 kommentar(er)
