Dual-acting compounds that deliver an acidifying domain via zanamivir to the virus surface are potent influenza inhibitors.

Dual-acting influenza inhibitors that deliver a proton-rich acidifying domain to the virion surface via zanamivir show exceptional antiviral activity in vitro and in vivo.

• Why it matters: Current antiviral design often targets fixed viral sites, but entry can be blocked by changing the virion surface microenvironment to prevent hemagglutinin receptor engagement.
• What they did: The study designed compounds to create a proton-rich mantle above influenza virions and tested effects on hemagglutinin interaction with cellular receptors, then evaluated antiviral activity in vitro and in vivo.
• The result: After a single dose, compounds protected ferrets and mice against influenza illness when given therapeutically or prophylactically, supporting this surface-acidification strategy for potent inhibition.

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