Human single-chain antibodies neutralize SARS-CoV-2 variants by engaging an essential epitope of the spike: a new weapon against COVID-19

Minenkova, O.; Santapaola, D.; Milazzo, F. M.; Anastasi, A.; Battistuzzi, G.; Chiapparino, C.; Rosi, A.; Gritti, G.; Borleri, G.; Rambaldi, A.; Dental, C.; Viollet, C.; Pagano, B.; Salvini, L.; Marra, E.; Luberto, L.; Rossi, A.; Riccio, A.; Merlo Pich, E.; Santoro, M. G.; De Santis, R.

doi:10.1101/2021.06.04.447066

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bioRxiv · 10.1101/2021.06.04.447066

Human single-chain antibodies neutralize SARS-CoV-2 variants by engaging an essential epitope of the spike: a new weapon against COVID-19

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Abstract

As of October 2021, coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global emergency, and novel therapeutics are urgently needed. Here we describe human single chain variable fragment (scFv) antibodies (76clAbs) that block an epitope of the SARS-CoV-2 spike protein essential for ACE2-mediated entry into cells. 76clAbs neutralize the delta variant and other variants being monitored (VBMs) and inhibit spike-mediated pulmonary cell-cell fusion, a critical feature of COVID-19 pathology. In two independent animal models, intranasal administration counteracted the infection. Due to high efficiency, remarkable stability, resilience to nebulization and low production cost, 76clAbs may become a relevant tool for rapid, self-administrable early intervention in SARS-CoV-2-infected subjects independently of their immune status.

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Minenkova, O., Santapaola, D., Milazzo, F. M., Anastasi, A., Battistuzzi, G., Chiapparino, C., Rosi, A., Gritti, G., Borleri, G., Rambaldi, A., Dental, C., Viollet, C., Pagano, B., Salvini, L., Marra, E., Luberto, L., Rossi, A., Riccio, A., Merlo Pich, E., Santoro, M. G., De Santis, R.. 2021-06-04. Human single-chain antibodies neutralize SARS-CoV-2 variants by engaging an essential epitope of the spike: a new weapon against COVID-19. https://doi.org/10.1101/2021.06.04.447066

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