Elsevier

Antiviral Research

Volume 93, Issue 1, January 2012, Pages 118-125
Antiviral Research

In vitro anti-hepatitis B and SARS virus activities of a titanium-substituted-heteropolytungstate

https://doi.org/10.1016/j.antiviral.2011.11.003Get rights and content

Abstract

A structural determined heteropolytungstate, [K4(H2O)8Cl][K4(H2O)4PTi2W10O40]·NH2OH 1, has been synthesized and evaluated for in vitro antiviral activities against hepatitis B (HBV) and SARS virus. The identity and high purity of compound 1 were confirmed by elemental analysis, NMR, IR analysis and single-crystal X-ray diffraction. The compound 1, evaluated in HepG 2.2.15 cells expressing permanently HBV, significantly reduced the levels of HBV antigens and HBV DNA in a dose-dependent and time-dependent manner. EC50 values were determined to be 54 μM for HBeAg, 61 μM for HBsAg and 2.66 μM for supernatant HBV DNA, as compared to 1671, 1570, 169 μM, respectively, for the commercially-available hepatitis B drug adefovir dipivoxil (ADV). Intracellular cccDNA, pgRNA and HBcAg were also found to be decreased by compound 1 in a concentration-dependent manner. Cytotoxicity results showed that compound 1 has low toxicity in HepG 2 cells with CC50 value of 515.20 μM. The results indicate that compound 1 can efficiently inhibit HBV replication in HepG 2.2.15 cells line in vitro. Additionally, compound 1 also shows high anti-SARS activity at an EC50 of 7.08 μM and toxicity with a CC50 of 118.6 μM against MDCK cells.

Highlights

► A structural determined heteropolytungstate has been synthesized. ► The heteropolytungstate can efficiently inhibit HBV replication in vitro. ► The heteropolytungstate also shows high anti-SARS virus activity in vitro.

Abbreviations

HBV
hepatitis B virus
INF-α
interferon alpha
3TC
nucleoside analog lamivudine
POMs
Polyoxometalates
SARS
severe acute respiratory syndrome
DMEM
Dulbecco’s Modified Eagle’s Medium
FBS
fetal bovine serum
Vero-E6
African green monkey kidney cells
MTT
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
ADV
adefovir dipivoxil
CC50
50% cytotoxic dose
TI
therapeutic index
EC50
50% effective concentration
CC0
maximal noncytotoxic concentration
EC90
90% effective concentration
MDCK
Madin–Darby canine kidney

Keywords

Heteropolytungstate
Antiviral activity
Hepatitis B virus
SARS virus
In vitro

Cited by (0)

1

These authors contributed equally to this study.

View Abstract