PROS1 and influenza: We now show that nitazoxanide selectively interferes with SARS-CoV-2 S glycoprotein biosynthesis, while it does not affect the expression of the other SARS-CoV-2 structural proteins N, E and M. We find that, as in the case of influenza and parainfluenza fusion proteins, nitazoxanide hampers the spike protein maturation at an Endo-H-sensitive stage, thus preventing its final processing, and resulting in inhibition of the S glycoprotein fusion activity during entry, as well as of syncytia formation due to S-driven cell–cell fusion.