It was demonstrated that several 5′-phosphonates of 4′-thio-5-ethyl-2′-deoxyuridine possessed antiviral activity in vitro and in the murine model of herpes simplex virus type 1 infection. It was shown that the derivatives after intraabdominal administration penetrated effectively into the brain tissue. The agents provided statistically significant increase of the average life span, tower virus titre in the brain and lower lethality when compared to the control group of the animals. It is emphasized that the derivatives were less toxic than the original compound.