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Potent neutralization of SARS-CoV-2 variants of concern by an antibody with an uncommon genetic signature and structural mode of spike recognition #MMPMID34592170
Kramer KJ; Johnson NV; Shiakolas AR; Suryadevara N; Periasamy S; Raju N; Williams JK; Wrapp D; Zost SJ; Walker LM; Wall SC; Holt CM; Hsieh CL; Sutton RE; Paulo A; Nargi RS; Davidson E; Doranz BJ; Crowe JE Jr; Bukreyev A; Carnahan RH; McLellan JS; Georgiev IS
Cell Rep 2021[Oct]; 37 (1): 109784 PMID34592170show ga
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages that are more transmissible and resistant to currently approved antibody therapies poses a considerable challenge to the clinical treatment of coronavirus disease (COVID-19). Therefore, the need for ongoing discovery efforts to identify broadly reactive monoclonal antibodies to SARS-CoV-2 is of utmost importance. Here, we report a panel of SARS-CoV-2 antibodies isolated using the linking B cell receptor to antigen specificity through sequencing (LIBRA-seq) technology from an individual who recovered from COVID-19. Of these antibodies, 54042-4 shows potent neutralization against authentic SARS-CoV-2 viruses, including variants of concern (VOCs). A cryoelectron microscopy (cryo-EM) structure of 54042-4 in complex with the SARS-CoV-2 spike reveals an epitope composed of residues that are highly conserved in currently circulating SARS-CoV-2 lineages. Further, 54042-4 possesses uncommon genetic and structural characteristics that distinguish it from other potently neutralizing SARS-CoV-2 antibodies. Together, these findings provide motivation for the development of 54042-4 as a lead candidate to counteract current and future SARS-CoV-2 VOCs.
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Cell+Rep 2021 ; 37 (1): 109784
