Increased in vitro Anti‐HIV Activity of Caffeinium‐Functionalized Polyoxometalates

Polyoxometalates (POMs), molecular metal oxide anions, are inorganic clusters with promising antiviral activity. Herein we report increased anti‐HIV‐1 activity of a POM when electrostatically combined with organic counter‐cations. To this end, Keggin‐type cerium tungstate POMs have been combined with organic methyl‐caffeinium (Caf) cations, and their cytotoxicity, antiviral activity and mode of action have been studied. The novel compound, Caf(4)K[β(2)‐CeSiW(11)O(39)]×H(2)O, exhibits sub‐nanomolar antiviral activity and inhibits HIV‐1 infectivity by acting on an early step of the viral infection cycle. This work demonstrates that combination of POM anions and organic bioactive cations can be a powerful new strategy to increase antiviral activity of these inorganic compounds.