Human inhalable antibody fragments neutralizing SARS-CoV-2 variants for COVID-19 therapy

Minenkova, Olga; Santapaola, Daniela; Milazzo, Ferdinando Maria; Anastasi, Anna Maria; Battistuzzi, Gianfranco; Chiapparino, Caterina; Rosi, Antonio; Gritti, Giuseppe; Borleri, Gianmaria; Rambaldi, Alessandro; Dental, Clélia; Viollet, Cécile; Pagano, Bruno; Salvini, Laura; Marra, Emanuele; Luberto, Laura; Rossi, Antonio; Riccio, Anna; Pich, Emilio Merlo; Santoro, Maria Gabriella; De Santis, Rita

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.