Keggin-Type Polyoxometalates as a Systematic Antiviral Scaffold: Activity, Cytotoxicity, and Solution Stability across Heteroion and Addenda Metal Variations.

Polyoxometalates (POMs) are promising antiviral agents, yet systematic structure-activity relationships remain scarce and biological stability is rarely assessed. Here we report the antiviral activity, cytotoxicity, and solution speciation of 11 Keggin-type POMs spanning three compositional series─PVxW12-x, PVxMo12-x, and SiMoxW12-x (x = 0-3)─alongside lacunary derivatives, and simple metal salt controls. Multinuclear NMR spectroscopy (31P, 51V, 183W) in cell culture medium under assay conditions revealed a direct correlation between cluster integrity and antiviral potency: compounds that decompose are uniformly inactive while structurally stable or partially transformed clusters show concentration-dependent inhibition. The silicomolybdotungstate series proved most promising, with [SiW12O40]4- and [SiMoW11O40]4- achieving IC50 values of 26.0 and 24.9 μM against HCoV-OC43. Antiviral potency correlates with overall cluster charge, with 4- anions consistently outperforming their 3- and 6- analogues─an observation rationalized through the superchaotropic ion concept.