Promising small moleculars – dispiroalkanes exhibited high effectiveness against human cytomegalovirus.

Many pathogenic viruses, including herpesviruses, SARS -Cov-2, cytomegalovirus, papillomavirus, virus Nipah and others, use the similar mechanism to join the target cells, which consists in their attachment to heparan sulfate proteoglycan of the cell membrane. If they fail to do that, the infection will be stopped. Scientists of the The Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences created a range of diazadispiroalkane derivatives,  which can become universal antivirals due to blocking of this mechanism, and one of them successfully passed preclinical studies as a drug for prevention and treatment of SARS-Cov-2.  Now the scientists have successfully tested the work of promising  compounds against new herpesvisuses. The results were published in the magazine Antiviral Research.

Human cytomegalovirus (the same as human herpesvirus -5) settles in salivary glands, whereby for the healthy organism the infection can pass unnoticed. However by transplantation, HIV and other conditions connected with weakening of the immune system, it can threaten patient’s life, especially it concerns new born babies. The virus of simplex herpes – 1 ( VSH -1) causes the “cold on the lips” – bubles on the skin and mucous membrane. Scientists of the The Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences together with collegues from  Institute of Virology by Medical Centre Charite in Berlin tested promising new compounds against murine strain of cytomegalovirus, human cytomegalovirus and herpesvirus -1.

«Previously we have published the article about two diazadispiroalkane derivatives, that exhibit activity against cytomegalovirus and pseudorabies virus, that causes Aujeszky’s disease among pigs and other species of domestic and wild animals. In our new work we have analyzed how these two compounds work against other herpesviruses, in order to find out more about potential medical activity of diazaspiroalkanes in general”, – tells the lead author of the work Vadim Makarov, Dr.Sci. (Pharmacy), Head of Laboratory of Biomedical Chemistry in The Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences.

Diazadispiroalkane derivatives are the small molecules, that have rings with positively charged nitrogen atoms in their structure. These ions draw to negatively charged heparan sulfate proteoglycans on the cell wall, anticipating viruses that also tend to attach to this “weak link” of the defense. Thus small molecules act very selectively, both preventing viruses to infect the first “victims”, and to spread on other cells. Besides, according to researches made on mice, compounds of this group have low toxicity for mammals.

One of such compounds, PDSTR, can become an innovative drug against SARS-Cov-2. In this role potential drug in the nearest time will pass clinical investigation. Besides this, molecule PDSTP turned out to be active against virus, causing corneal inflammation among rabbits.  Due to its mechanism of action  such drugs could become universal. During new research the tests proved the activity of PDSTP and “relative” molecule DSTP -27 against herpesviruses.

”Interestingly enough, that compounds PDSTR and DSTP – 27 reduced the levels of protein synthesis from viral genes in cells infected by HSV-1 and cytomegaloviruses, according to dosage. We suppose that both small molecules interacted electrostatically with proteoglycans, protecting the parts, that glycoproteins on the surface of herpesviruses could attach to. Moreover, both conpounds turned effective against transferring HSV-1 and human cytomegalovirus from one cells to others.  All this make these molecules promising drugs, that can become a milestone in antiviral therapy”, – concludes Vadim Makarov.