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Human adenoviruses, in particular D8, D19, and D37, cause ocular infections. Currently, there is no available causally directed treatment, which efficiently counteracts adenoviral infectious diseases. In our previous work, we showed that gene silencing by means of RNA interference is an effective approach for downregulation of human species D adenoviruses replication. In this study, we compared the biological activity of siRNAs and their modified analogs targeting human species D adenoviruses DNA polymerase. We found that one of selectively 2'-O-methyl modified siRNAs mediates stable and long-lasting suppression of the target gene (12 days post transfection). We suppose that this siRNA can be used as a potential therapeutic agent against human species D adenoviruses.

A systematic analysis of DNA polymerase of human herpes simplex type 1 virus, cytomegalovirus, and human type 2 adenovirus with the help of a broad set of modified substrates of these enzymes has been carried out. It revealed compounds capable of inhibiting the DNA synthesis catalyzed both by all three enzymes and DNA polymerase alpha from human placenta. Compounds have been found which effectively and specifically inhibit the DNA synthesis catalyzed by some of the abovementioned enzymes. It has been shown that the molecular mechanism of inhibition consists either in the termination of DNA elongation or in inhibition without incorporation into the growing DNA chain.