Vol 63, No 5 (2018)

Modern chemotherapy of cytomegalovirus (CMV) infections has a very limited arsenal of first-line drugs. These are preparations of ganciclovir (GCV) belonging to the class of modified nucleosides and its metabolic precursor ganciclovir valine ester. After three-step phosphorylation, GCV, as a structural analogue of the natural nucleotide, competes with it for binding to DNA polymerase and, due to its structural features, inhibits its activity. However, with prolonged use of GCV, mainly under conditions of immunosuppression, the virus develops drug resistance associated in most cases with changes in pUL97 catalyzing the first stage of GCV phosphorylation, as well as in the catalytic subunit of DNA polymerase. When variants of viruses resistant to GCV appear, second-line drugs are used: pyrophosphate analog of foscarnet and nucleotide cidofovir. Resistance to second-line drugs is due to mutations in the pol-gene and in a number of cases leads to multiresistance, which makes it impossible to use traditional anti-CMV drugs. In addition, the use of all of the above drugs is accompanied by the development of severe side effects. All of the above determines the need to search for new compounds that can effectively inhibit the reproduction of the virus, harmless to the macroorganism, convenient to use, overcoming the drug resistance barrier in viruses. As a result of the search in international databases (PubMed, MedLine, eLIBRARY.RU, ClinicalTrials.gov, etc.), the main trends in the search for new anti-CMV agents were identified. In the first part of the review, we concentrated on compounds that are modifications of known antiviral agents currently used in clinical practice, the most promising for the development of drug anti-CMV drugs.

Increased protease activity and a significant amount of granzyme B were observed in in organs of mice infected with acute herpes simplex virus HSV-1 with the introduction of Stimforte (100 or 250 µg/mouse). Thus, this drug activates killer cells, which play an extremely important role in the suppression of HSV-1 infection. Although the administration of Stimforte (100 μg/mouse) to intact mice results in the activation of IFN-β production and does not activate the production of IFN-λ, Stimforte administration to animals infected with HSV-1 reduces production of IFN-β in serum, brain and lungs, whereas the production of IFN-λ considerably increases as the result of administration of 100 μg/mouse of Stimforte.

The etiological structure of influenza and other acute respiratory viral infections including their rate of incidence in St. Petersburg and Leningrad region during 4 epidemic seasons has been studied. Seasonality of some respiratory viruses was shown and peaks of circulation of RSV, adenovirus, parainfluenza viruses, rhinovirus, bocavirus, metapneumovirus and coronavirus were marked. The interference of influenza A viruses and RSV, RSV and rhinoviruses was highlighted. A high incidence of adenovirus infection in organized communities and RSV infection in children was revealed.