FIGURE 1.

Examples of selection strategies used in deep mutational scans of viral spike proteins. (A) Infectious virus variants (green) are enriched after passaging through a permissive cell line expressing host target receptors (blue). (B) Syncytia are enriched upon fusion of cells expressing variants of viral fusion protein (pale yellow cells) and cells expressing the entry receptor (pale blue cells) in the presence of two different antibiotics. (C) Soluble extracellular domains of the viral spike are displayed on the yeast cell wall via Aga1p–Aga2p (dark red). After fluorescence activated cell sorting (FACS), these viral proteins (green) are enriched if they possess high binding affinity and/or expression to fluorescent partners, such as soluble receptors (blue). (D) After FACS, mammalian cells expressing viral spike proteins (green) are enriched if they are highly expressed and bind with high affinity to fluorescently labeled antibodies (pink) or soluble receptors.