New effective chemically synthesized anti-smallpox compound NIOCH-14
Autor: | E. L. Zavjalov, Oleg Yu Mazurkov, A. A. Sergeev, Alexey Ya. Tikhonov, Bulychev Le, Sergeev An, Larisa N. Shishkina, Darya O. Galahova, A. S. Kabanov, Boris A. Selivanov, N. I. Bormotov, Alexander A. Sergeev, O. S. Taranov, K. A. Titova, Alena S. Ovchinnikova, Alexander P. Agafonov, Maria A Skarnovich, Skarnovich Mo |
---|---|
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Male viruses 030106 microbiology Mice SCID Biology Isoindoles Antiviral Agents Virus 03 medical and health sciences Monkeypox Mice In vivo Oral administration Virology Chlorocebus aethiops medicine Animals Dicarboxylic Acids Monkeypox virus Vero Cells Mice Inbred ICR Molecular Structure Ectromelia virus Lethal dose virus diseases Variola virus medicine.disease biology.organism_classification Marmota Benzamides Nasal administration Female Smallpox |
Zdroj: | The Journal of general virology. 97(5) |
ISSN: | 1465-2099 |
Popis: | Antiviral activity of the new chemically synthesized compound NIOCH-14 (a derivative of tricyclodicarboxylic acid) in comparison with ST-246 (the condensed derivative of pyrroledione) was observed in experiments in vitro and in vivo using orthopoxviruses including highly pathogenic ones. After oral administration of NIOCH-14 to outbred ICR mice infected intranasally with 100 % lethal dose of ectromelia virus, it was shown that 50 % effective doses of NIOCH-14 and ST-246 did not significantly differ. The ‘therapeutic window’ varied from 1 day before infection to 6 days post-infection (p.i.) to achieve 100–60 % survival rate. The administration of NIOCH-14 and ST-246 to mice resulted in a significant reduction of ectromelia virus titres in organs examined as compared with the control and also reduced pathological changes in the lungs 6 days p.i. Oral administration of NIOCH-14 and ST-246 to ICR mice and marmots challenged with monkeypox virus as compared with the control resulted in a significant reduction of virus production in the lungs and the proportion of infected mice 7 days p.i. as well as the absence of disease in marmots. Significantly lower proportions of infected mice and virus production levels in the lungs as compared with the control were demonstrated in experiments after oral administration of NIOCH-14 and ST-246 to ICR mice and immunodeficient SCID mice challenged with variola virus 3 and 4 days p.i., respectively. The results obtained suggest good prospects for further study of the chemical compound NIOCH-14 to create a new smallpox drug on its basis. |
Databáze: | OpenAIRE |
Externí odkaz: |