Mixed viral infection is one of the current and unexplored issues of human infectious diseases. A special place in the development of these pathologies is occupied by adeno- and herpes viruses that are able to persist for a long time in a latent condition in the body. There is a huge lack of knowledge about antiviral activities of specific drugs during the mixed infections. The study of know drugs and discovery of new compounds using not only standard mono-infections but also with created mixed infections is a topical and a new direction in antivirus screening. Previously in our department, the models of adeno-herpetic infections in cells of different origins were created and the features of the development of viral infections in these systems were studied.
The model of simultaneous adeno-herpetic infection of MDBK cells was used for the analysis of the antiherpetic drug acyclovir (ACV) and for research of new fluorine-containing derivatives of L-phenylalanine (10S-23 and 10S-24, synthesized in Institute of Organic Chemistry of the NAS of Ukraine). Determination of the antiviral activity accessed via real-time PCR and infectious virus yield reduction assay demonstrated the inhibitory effect of these compounds on the late stage of the HSV-1 and HAdV5 reproduction. With the presence of 10S-24 and ACV in the conditions of mono-infection, HSV-1 DNA replication was inhibited on 39 and 100%, respectively. Furthermore, the significant delays of HSV-1 reproductions were observed, the titer of virus obtained de novo reduces on >99%. It was shown that for adenovirus infection of the cells, all compounds reduced the titer of the virus on 34-96%.
Use of the ACV under mixed infection led to the 46% loss of the drug activity against HSV-1. The application of 10S-23 and 10S-24 at mixed infection induced a decrease of effectiveness of the compounds relatively herpes simplex virus by 58-73% and 16-57%, respectively. It was shown that compounds have been not effective against HAdV5 under conditions of co-infection of cells.
An abnormal action of drugs in co-infected cells indicates the need for further study of the mechanisms and targets of antiviral activity of compounds in such conditions, because using these compounds can be ineffective in medical practice.
Acknowledgements
This work was supported by a President’s of Ukraine grant for competitive projects F70 of the State Fund for Fundamental Research.
