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Kramer, Kevin J.; Johnson, Nicole V.; Shiakolas, Andrea R.; Suryadevara, Naveenchandra; Periasamy, Sivakumar; Raju, Nagarajan; Williams, Jazmean K.; Wrapp, Daniel; Zost, Seth J.; Walker, Lauren M.; Wall, Steven C.; Holt, Clinton M.; Hsieh, Ching-Lin; Sutton, Rachel E.; Paulo, Ariana; Nargi, Rachel S.; Davidson, Edgar; Doranz, Benjamin J.; Crowe, James E.; Bukreyev, Alexander; Carnahan, Robert H.; McLellan, Jason S.; Georgiev, Ivelin S.
Cell reports (Cambridge), 10/2021, Letnik: 37, Številka: 1Journal Article
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. Display omitted •LIBRA-seq identifies 54042-4, a potently neutralizing SARS-CoV-2 antibody•54042-4 maintains potent neutralization against Alpha, Beta, Gamma, and Delta VOCs•The epitope of 54042-4 is highly conserved among current SARS-CoV-2 isolates Kramer et al. demonstrate that antibody 54042-4 recognizes residues highly conserved across global SARS-CoV-2 isolates. Antibody 54042-4 potently neutralizes all known circulating variants of concern (VOCs) and could be developed as a clinical candidate to treat COVID-19 infection.
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in: SICRIS
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