Potent neutralization of SARS-CoV-2 variants of concern by an antibody with a unique genetic signature and structural mode of spike recognition

Kramer, K. J.; Johnson, N. V.; Shiakolas, A. R.; Suryadevara, N.; Periasamy, S.; Raju, N.; Williams, J. K.; Wrapp, D.; Zost, S. J.; Holt, C. M.; Hsieh, C.-L.; Sutton, R. E.; Paulo, A.; Davidson, E.; Doranz, B. J.; Crowe, J. E.; Bukreyev, A.; Carnahan, R. H.; McLellan, J. S.; Georgiev, I. S.

doi:10.1101/2021.05.16.444004

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bioRxiv · 10.1101/2021.05.16.444004

Potent neutralization of SARS-CoV-2 variants of concern by an antibody with a unique genetic signature and structural mode of spike recognition

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Abstract

The emergence of novel SARS-CoV-2 lineages that are more transmissible and resistant to currently approved antibody therapies poses a considerable challenge to the clinical treatment of 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 LIBRA-seq technology from an individual who recovered from COVID-19. Of these antibodies, 54042-4 showed potent neutralization against authentic SARS-CoV-2 viruses, including variants of concern (VOCs). A cryo-EM structure of 54042-4 in complex with the SARS-CoV-2 spike revealed an epitope composed of residues that are highly conserved in currently circulating SARS-CoV-2 lineages. Further, 54042-4 possesses unique genetic and structural characteristics that distinguish it from other potently neutralizing SARS-CoV-2 antibodies. Together, these findings motivate 54042-4 as a lead candidate for clinical development to counteract current and future SARS-CoV-2 VOCs.

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Kramer, K. J., Johnson, N. V., Shiakolas, A. R., Suryadevara, N., Periasamy, S., Raju, N., Williams, J. K., Wrapp, D., Zost, S. J., Holt, C. M., Hsieh, C.-L., Sutton, R. E., Paulo, A., Davidson, E., Doranz, B. J., Crowe, J. E., Bukreyev, A., Carnahan, R. H., McLellan, J. S., Georgiev, I. S.. 2021-05-16. Potent neutralization of SARS-CoV-2 variants of concern by an antibody with a unique genetic signature and structural mode of spike recognition. https://doi.org/10.1101/2021.05.16.444004

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