title: New effective chemically synthesized anti-smallpox compound NIOCH-14.
abstract: 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.
authors: State Research Center of Virology and Biotechnology Vector (SRC VB Vector),Koltsovo, Novosibirsk region,Russian Federation.
authors: Oleg Yu
authors: OY
authors: Mazurkov
authors: State Research Center of Virology and Biotechnology Vector (SRC VB Vector),Koltsovo, Novosibirsk region,Russian Federation.
authors: Alexey S
authors: AS
authors: Kabanov
authors: State Research Center of Virology and Biotechnology Vector (SRC VB Vector),Koltsovo, Novosibirsk region,Russian Federation.
authors: Larisa N
authors: LN
authors: Shishkina
authors: State Research Center of Virology and Biotechnology Vector (SRC VB Vector),Koltsovo, Novosibirsk region,Russian Federation.
authors: Alexander A
authors: AA
authors: Sergeev
authors: State Research Center of Virology and Biotechnology Vector (SRC VB Vector),Koltsovo, Novosibirsk region,Russian Federation.
authors: Maksim O
authors: MO
authors: Skarnovich
authors: State Research Center of Virology and Biotechnology Vector (SRC VB Vector),Koltsovo, Novosibirsk region,Russian Federation.
authors: Nikolay I
authors: NI
authors: Bormotov
authors: State Research Center of Virology and Biotechnology Vector (SRC VB Vector),Koltsovo, Novosibirsk region,Russian Federation.
authors: Maria A
authors: MA
authors: Skarnovich
authors: State Research Center of Virology and Biotechnology Vector (SRC VB Vector),Koltsovo, Novosibirsk region,Russian Federation.
authors: Alena S
authors: AS
authors: Ovchinnikova
authors: State Research Center of Virology and Biotechnology Vector (SRC VB Vector),Koltsovo, Novosibirsk region,Russian Federation.
authors: Ksenya A
authors: KA
authors: Titova
authors: State Research Center of Virology and Biotechnology Vector (SRC VB Vector),Koltsovo, Novosibirsk region,Russian Federation.
authors: Darya O
authors: DO
authors: Galahova
authors: State Research Center of Virology and Biotechnology Vector (SRC VB Vector),Koltsovo, Novosibirsk region,Russian Federation.
authors: Leonid E
authors: LE
authors: Bulychev
authors: State Research Center of Virology and Biotechnology Vector (SRC VB Vector),Koltsovo, Novosibirsk region,Russian Federation.
authors: Artemiy A
authors: AA
authors: Sergeev
authors: State Research Center of Virology and Biotechnology Vector (SRC VB Vector),Koltsovo, Novosibirsk region,Russian Federation.
authors: Oleg S
authors: OS
authors: Taranov
authors: N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry (NIOCH),Novosibirsk,Russian Federation.
authors: Boris A
authors: BA
authors: Selivanov
authors: N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry (NIOCH),Novosibirsk,Russian Federation.
authors: Alexey Ya
authors: AY
authors: Tikhonov
authors: Institute of Cytology and Genetics (ICG),Novosibirsk,Russian Federation.
authors: Evgenii L
authors: EL
authors: Zavjalov
authors: State Research Center of Virology and Biotechnology Vector (SRC VB Vector),Koltsovo, Novosibirsk region,Russian Federation.
authors: Alexander P
authors: AP
authors: Agafonov
authors: State Research Center of Virology and Biotechnology Vector (SRC VB Vector),Koltsovo, Novosibirsk region,Russian Federation.
authors: Alexander N
authors: AN
authors: Sergeev
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D001549:Benzamides / Q000138:chemical synthesis / Q000494:pharmacology; D002522:Chlorocebus aethiops; D003998:Dicarboxylic Acids / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D054833:Isoindoles / Q000138:chemical synthesis / Q000494:pharmacology; D008297:Male; D008392:Marmota; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D015394:Molecular Structure; D045908:Mpox, Monkeypox / Q000188:drug therapy*; D008993:Monkeypox virus; D012899:Smallpox / Q000188:drug therapy*; D012901:Variola virus; D014709:Vero Cells; D010797:Phthalimides
chemical_list: D000998:Antiviral Agents; D001549:Benzamides; D003998:Dicarboxylic Acids; D054833:Isoindoles; C000618192:NIOCH-14; C505045:tecovirimat; D010797:Phthalimides