THE STUDY OF TOXICITY AND THE PROTECTIVE PROPERTIES OF IFN-A2B WITH ANTIOXIDANTS AND SPECIFIC ANTIVIRAL CHEMO DRUGS FOR HERPES VIRAL INFECTIONS "IN VITRO" AND "IN VIVO"

Abstract

Herpes simplex virus-1 (HSV1) and cytomegalovirus (CMV) are extremely widespread in the human population and can affect various organs and tissues. HSV1 and CMV infections are particularly dangerous for pregnant women and newborns. The main disadvantages of antiviral chemotherapeutic agents are their high toxicity, limited bioavailability and the development of drug resistance during the long-term tretatment. Currently the search for new drugs and new regimens which permit to avoid the adverse manifestations of toxic effects while maintenance of high antiviral efficacy is performed. The purpose of this study was to evaluate the effectiveness of the of scheme of multimodal therapy of herpes virus infection with a new drug form (NDF) VIFERON®, a solution for local application in combination with specific antiviral chemo drugs "in vitro" and "in vivo". For the first time the use of NDF in a concentration of 20000 IU/ml was found to inhibit CMV infection by 83% in a therapeutic scheme “in vitro”. NDF has been shown to increase the specific antiviral activity of chemotherapy, allowing to significantly reduce the effective inhibitory concentration for Acyclovir - by 3 times, for Acyclovir - by 20 times. In “in vivo” experiments NDF has not demonstrated any toxic effect on the animal organism. 24 h after intraperitoneal infection of mice HSV1 the single administration of NDF protects 60% of the animals from lethal (20 LD5o) herpes virus infection. Combined use of ТДА and ACV therapeutic scheme “in vivo” allowed: a) reduce the dose of both drugs by 10 times (up to 2000 IU/ml and 5 mg/kg, respectively) compared with either single agent; and b) to achieve the therapeutic effect with the use of the short regimen - 3 days; c) to provide full protection (100%) animals from lethal HSV1-infection (20 LD50). The high protective effect of multimodal therapy of lethal herpes virus infection “in vivo” was provided due to the synergistic character of the interaction of drugs used.