Antiviral activity of the organic germanium complex with aciclovir against herpes simplex virus (Herpesviridae: Alphaherpesvirinae: Simplexvirus: Human alphaherpesvirus 1/2) in the in vitro and in vivo systems

Abstract

A significant increase in the incidence of various forms of herpesvirus infection (HVI) determines the need to search for new approaches to the modification of one of the basic antiviral drugs aciclovir (ACV) and its dosage forms to improve their biopharmaceutical characteristics and increase the effectiveness of therapy. In this aspect, an innovative organic germanium complex with aciclovir (OGCA) is promising.The aim of the study was to assess the antiviral activity of OGCA against the herpes simplex virus (HSV) (human herpes virus, HHV) on the HVI models both in vitro and in vivo. We studied the activity of OGCA in a therapeutic regimen against HSV-1 (HHV-1) (Kl strain), HSV-2 (HHV-2) (VN strain) using virological and statistical research methods in the in vitro model of HVI on Vero cell culture and the model of genital herpes (GH) caused by HHV-2 (VN strain) in male guinea pigs (Canis porcellus). It was found OGCA inhibits the replication of HHV-1 and HHV-2 in Vero cells, and has anti-HHV activity in the GH model in male guinea pigs, leading to a decrease in the severity and duration of the disease, the intensity and duration of viral shedding. The most pronounced activity was detected when preparation was applied topically 5 times a day for 5 days at the early stages of infection (3% gel). The delayed use of OGCA (48 hours after infection) also had statistically significant efficacy compared to commercial reference drugs containing aciclovir or its pro-drugs: aciclovir (5% cream), AIL (acyclovir+interferon alfa-2b+lidocaine, 3% ointment), penciclovir (1% cream). OGCA significantly reduced the number of days of the pathogen shedding, as well as its infectivity, compared to animals in the control group and ones receiving placebo. The activity of OGCA, apparently, is due to its improved biopharmaceutical characteristics compared to aciclovir, as well as the presence of a number of biological activities of its constituent components. The results of the study allow us to consider OGCA as the basis for the development of antiviral agents for the treatment of HVI.