Efficient in vitro Inhibition of Herpes Simplex Virus Type 1 Replication with Oligonucleotide-Containing Nanocomposites

The control of herpesvirus infections is a pressing public health issue because of the widespread prevalence of herpes simplex virus (HSV), which causes a variety of diseases ranging from mild primary skin lesions to severe and sometimes fatal encephalitis. The use of antisense oligonucleotides (ONs) to suppress HSV replication is a promising development in this field. To overcome one of the major obstacles in the delivery of ONs into cells, we have prepared nanocomposites consisting of antisense oligonucleotides immobilized on titanium dioxide nanoparticles in the form of anatase (Ans ~ ON). We have investigated the antiviral activity of several nanocomposites bearing oligonucleotides targeting different regions of the HSV-1 genome. Unmodified oligonucleotides and oligonucleotides with methylsulfonyl phosphoramidate internucleotide groups have been used in the work. The most effective nanocomposites reduced viral replication in the cell culture by 3–3.5 orders of magnitude. The selectivity index values of these nanocomposites have been evaluated as 90–110 in the post-infection mode.