Novel sialidase inhibitors suppress mumps virus replication and infection.

This article focuses on the development and evaluation of three novel sialidase inhibitors—DANA derivatives named Compounds 1, 2, and 3—that specifically target the hemagglutinin-neuraminidase (HN) sialidase of mumps virus (MuV; orthorubulavirus parotitidis). These compounds exhibit greater inhibitory potency and specificity against MuV sialidase activity and viral replication in vitro compared to the known inhibitor DANA (2,3-didehydro-2-deoxy-N-acetylneuraminic acid), without cytotoxicity. The inhibitors also impede viral hemagglutination and infection, likely by interfering with the single functional site of MuV-HN responsible for both receptor binding and sialidase activity. The study highlights the structural basis for enhanced inhibition via hydrophobic modifications at the C4 position of DANA and suggests these compounds as promising leads for direct-acting antivirals against MuV, although further optimization and in vivo validation are needed.