Human inhalable antibody fragments neutralizing SARS-CoV-2 variants for COVID-19 therapy
Olga Minenkova, Daniela Santapaola, Ferdinando Maria Milazzo, Anna Maria Anastasi, Gianfranco Battistuzzi, Caterina Chiapparino, Antonio Rosi, Giuseppe Gritti, Gianmaria Borleri, Alessandro Rambaldi, Clélia Dental, Cécile Viollet, Bruno Pagano, Laura Salvini, Emanuele Marra, Laura Luberto, Antônio Rossi, Anna Riccio, Emilio Merlo Pich, Maria Gabriella Santoro, Rita De Santis
Abstract
As of December 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. Because of their high efficiency, remarkable stability, resilience to nebulization, and low cost of production, 76clAbs may become a relevant tool for rapid, self-administrable early intervention in SARS-CoV-2-infected subjects independently of their immune status.