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

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

doi:10.1016/j.ymthe.2022.02.013

BioengineeringbioRxivJun 4, 2021

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

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

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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