GBP2 and infection: Here we report that the interferon-inducible restriction factors GBP2 and 5 interfere with SARS-CoV-2 spike cleavage, and significantly inhibit infection by the early-lineage SARS-CoV-2 strains Wuhan-Hu-1 and VIC, but that previously dominant VOCs Alpha and Delta have evolved to evade GBP-mediated inhibition of infectivity.