Fig. 3: Protection against SARS-CoV-2 escape mutations generated over four viral passages.

a, Tabular representation of the CPEs induced by SARS-CoV-2 cultured in the presence of increasing concentrations of monovalent DARPin binder R2, multispecific DARPin antiviral ensovibep and the antibody antivirals REGN10933, REGN10987 and S309 or a cocktail of REGN10933 and REGN10987 through passage 1 to passage 4. Color code represents the highest concentration showing ≥20% CPE, for which the culture supernatants were passaged to the next round and deep sequenced for the identification of potential escape mutations. b, Identification of escape mutations in viral passages using deep sequencing. SARS-CoV-2 virus was serially passaged with the monovalent DARPin binder R2 and ensovibep. To identify putative escape mutations in the spike protein, RNA was extracted and sequenced from the supernatant of wells with the greatest selective pressure showing a substantial CPE. All variants in the spike protein relative to the reference genome (NC_045512.2) are shown. Passage 0 of the virus control corresponds to the inoculum used for all experiments. The color of the fields is proportional to the fraction of the reads containing the respective variant (red = 1.0, white = 0.0).