New effective chemically synthesized anti-smallpox compound NIOCH-14

New effective chemically synthesized anti-smallpox compound NIOCH-14 Full article

Journal

Journal of General Virology
ISSN: 0022-1317 , E-ISSN: 1465-2099

Output data

Year: 2016, Volume: 97, Pages: 1229-1239 Pages count : 11 DOI: 10.1099/jgv.0.000422

Authors

Mazurkov Oleg Yu. ¹ , Kabanov Alexey S. ¹ , Shishkina Larisa N. ¹ , Sergeev Alexander A. ¹ , Skarnovich Maksim O. ¹ , Bormotov Nikolay I. ¹ , Skarnovich Maria A. ¹ , Ovchinnikova Alena S. ¹ , Titova Ksenya A. ¹ , Galahova Darya O. ¹ , Bulychev Leonid E. ¹ , Sergeev Artemiy A. ¹ , Taranov Oleg S. ¹ , Selivanov Boris A. ² , Tikhonov Alexey Ya. ² , Zavjalov Evgenii L. ³ , Agafonov Alexander P. ¹ , Sergeev Alexander N. ¹

Affiliations

1	(Данные Web of science) State Res Ctr Virol & Biotechnol Vector, Koltsov, Novosibirsk Reg, Russia
2	(Данные Web of science) NN Vorozhtsov Novosibirsk Inst Organ Chem NIOCH, Novosibirsk, Russia
3	(Данные Web of science) Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia

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.

Mazurkov O.Y. , Kabanov A.S. , Shishkina L.N. , Sergeev A.A. , Skarnovich M.O. , Bormotov N.I. , Skarnovich M.A. , Ovchinnikova A.S. , Titova K.A. , Galahova D.O. , Bulychev L.E. , Sergeev A.A. , Taranov O.S. , Selivanov B.A. , Tikhonov A.Y. , Zavjalov E.L. , Agafonov A.P. , Sergeev A.N.
New effective chemically synthesized anti-smallpox compound NIOCH-14

Journal of General Virology. 2016. V.97. P.1229-1239. DOI: 10.1099/jgv.0.000422 WOS Scopus РИНЦ OpenAlex

Full text from publisher

Published print:

May 1, 2016

Web of science:	WOS:000375837800020
Scopus:	2-s2.0-84964977683
Elibrary:	27152425
OpenAlex:	W2301868282

DB	Citing
Web of science	52
Scopus	59
Elibrary	53
OpenAlex	66