Influenza A viruses (IAVs) cause recurrent epidemics in humans, with serious threat of lethal worldwide pandemics. The occurrence of
antiviral-resistant virus strains and the emergence of highly pathogenic influenza viruses have triggered an urgent need to develop new anti-IAV treatments. One compound found to inhibit IAV, and other
virus infections, is
saliphenylhalamide (
SaliPhe).
SaliPhe targets host
vacuolar-ATPase and inhibits acidification of endosomes, a process needed for productive
virus infection. The major obstacle for the further development of
SaliPhe as
antiviral drug has been its poor solubility. Here, we investigated the possibility to increase
SaliPhe solubility by loading the compound in thermally hydrocarbonized porous
silicon (THCPSi) nanoparticles.
SaliPhe-loaded nanoparticles were further investigated for the ability to inhibit
influenza A
infection in human retinal pigment epithelium and Madin-Darby canine kidney cells, and we show that upon release from THCPSi,
SaliPhe inhibited IAV
infection in vitro and reduced the amount of progeny virus in IAV-infected cells. Overall, the PSi-based nanosystem exhibited increased dissolution of the investigated anti-IAV
drug SaliPhe and displayed excellent in vitro stability, low cytotoxicity, and remarkable reduction of viral load in the absence of organic
solvents. This proof-of-principle study indicates that PSi nanoparticles could be used for efficient delivery of
antivirals to infected cells.