Polyoxometallates inhibit ZIKA virus by targeting the viral E protein

ENDERLE, ANA; BOLLINI, MARIELA; CULZONI, JULIA; GROSS, RÜDIGER; STREB, CARSTEN

Congreso; Annual International Remote Conference Science & Society; 2020

BackgroundZIKA virus (ZIKV) is a re-emerging pathogen that could cause several diseases such us meningoencephalitis, Guillain-Barré syndrome and microcephaly, for which no specific antiviral treatment so far exists. Polyoxometalates (POMs) are anionic clusters comprised of early transition metal (mostly Mo, V, and W) oxides exhibiting, as reported, anti-ZIKV activity. Here, we describe a new approach that combines experimental data and docking studies to investigate the mechanism of action of Dawson family of POMs on ZIKV.MethodsDawson-POMs were synthesized and purified according to published procedures and were characterized by FT-IR spectroscopy. Anti-ZIKV activity of POM was assessed by infecting VeroE6 cells and intracellular immunodetection of the ZIKV-E protein 2 days post infection. Toxicity of compounds was evaluated by CellTiter-Glo assay. Molecular docking studies were performed using AutoDock 4.2 software and Mercury CSD 4.0.0. The structures of the envelope protein of ZIKV and crystallographic models of POMs were from the RSC Protein Data Bank and CCDC database. DFT and Lamarckian genetic algorithm were employed for the calculations. ResultsAll D-POMs tested here were active against ZIKV-MR766, yielding IC 50 values ranging from 128.3 nM to 148.4 nM (0.55 μg/ml to 0.67 μg/ml). Time of addition and cell-virus experiments confirmed that the antiviral activity is exerted on the ZIKA virions. Blind docking to the entire E protein results showed two potential binding sites corresponding to the patch of residues ARG138, ARG164 y LYS166 (site 1) and the area around the fusion loop (99-110) (site 2), with the first being more favorable (70%) compared to the second. The second search for K6P2W18O62 was done to study interactions of 1:1 with two cleavage sites of the E-protein. The predicted binding free energies calculated are low -values of -9.3 for site 1 and -9.42 kcal/mol for site 2. The results showed two different binding sites where this POM is interacting with similar binding energies (fusion loop and positive patch regions). ConclusionIn conclusion, by combining molecular docking studies and biological assays we identified the potential binding site of W-Dawson POMs on the ZKV E protein, which could explain their antiviral activity. These results are expected to highlight the impact of POMs as antiviral compounds and their interaction with biomolecules.