Inhibition of Herpes Simplex Virus Type 1 Infection by Some Selected Antitumor Titanium(III)-Based Coordination Compounds

ABSTRACT

Using a standard plaque assay and clinical strains of Herpes Simplex virus type 1 (HSV 1), we have tested the ability of two titanium (Ti) - content complexes—Titanocene Dichloride (Cp₂TiCl₂) and Titanocene Y. Virus was treated by incubation at 37°C with both complexes in cell culture media and was then diluted and plated onto human embryonic lung fibroblast cells MRC-5 for detection and quantitation of remaining infectious virus. Of one randomly chosen clinical HSV 1 (TM strain), sensitive to acyclovir (ACV), was inactivated > 98% by treatment in vitro with 0.01 μM Titanocene Y for 2h. The effect was concentration dependent. With an HSV 1 strain, 0.01 μM Titanocene Y or Cp₂TiCl₂ caused 99% inactivation, 0.001μM caused 98 to 99% inactivation, and 0.0001μM caused 63 to 86% inactivation. Short (5 min) treatments of selected isolate with Titanocene Y or Cp₂TiCl₂ yielded inactivation rates of 0 to 55%. We assumed also that Titanocene Y or Cp₂TiCl₂ could be able to affect negatively not only virus DNA synthesis but also another virus target. The data obtained show that: (i) the 300bp relatively stable region during a short period of viral replication corresponding to ReIV is amplified in non-treated viral control, but not in mock cells and in negative control and (ii) the region was not amplified in Titanocene Y treated samples. The data show that the effect of the suppressive therapy of virus replication by Titanocene Y could be due to the suppression of immediate early Us1 and Us12 genes encoding essential for virus replication products α22—the protein affecting virus ability to replicate, and α47—the protein inhibiting MHC I antigen presentation.

Keywords:

• Herpes Simplex virus (HSV)
• inhibition
• Titanocene Dichloride (Cp₂TiCl₂)
• Titanocene Y