title: [THE USE OF THE MODEL MOUSE ICR--VARIOLA VIRUS FOR EVALUATION OF ANTIVIRAL DRUG EFFICACY].
abstract: Mice of the ICR outbred population were infected intranasally (i/n) with the variola virus (VARV, strain Ind-3a). Clinical signs of the disease did not appear even at the maximum possible dose of the virus 5.2 lg PFU/head (plaque-forming units per head). In this case, 50% infective dose (ID50) of VARV estimated by the presence or absence of the virus in the lungs three days after infection (p.i.) was equal to 2.7 ± 0.4 lg PFU/head. Taking into account the 10% application of the virus in the lungs during the intranasal infection of the mice, it was adequate to 1.7 lg PFU/lungs. This indicates a high infectivity of the VARV for mice comparable to its infectivity for humans. After the i/n infection of mice with the VARV at a dose 30 ID50/ head the highest concentration of the virus detected in the lungs (4.9 ± 0.0 lg PFU/ml of homogenate) and in nasal cavity tissues (4.8 ± 0.0 lg PFU/ml) were observed. The pathomorphological changes in the respiratory organs of the mice infected with the VARV appeared at 3-5 days p.i., and the VARV reproduction noted in the epithelial cells and macrophages were noticed. When the preparations ST-246 and NIOCH-14 were administered orally at a dose of 60 μg/g of mouse weight up to one day before infection, after 2 hours, 1 and 2 days p.i., the VARV reproduction in the lungs after 3 days p.i. decreased by an order of magnitude. Thus, outbred ICR mice infected with the VARV can be used as a laboratory model of the smallpox when evaluating the therapeutic and prophylactic efficacy of the antismallpox drugs.
authors.forename: K A
authors.initials: KA
authors.lastname: Titova
authors.forename: Al A
authors.initials: AA
authors.lastname: Sergeev
authors.forename: A S
authors.initials: AS
authors.lastname: Kabanov
authors.forename: L E
authors.initials: LE
authors.lastname: Bulychev
authors.forename: Ar A
authors.initials: AA
authors.lastname: Sergeev
authors.forename: D O
authors.initials: DO
authors.lastname: Galakhova
authors.forename: L N
authors.initials: LN
authors.lastname: Shishkina
authors.forename: A S
authors.initials: AS
authors.lastname: Zamedyanskaya
authors.forename: A E
authors.initials: AE
authors.lastname: Nesterov
authors.forename: A G
authors.initials: AG
authors.lastname: Glotov
authors.forename: O S
authors.initials: OS
authors.lastname: Taranov
authors.forename: V V
authors.initials: VV
authors.lastname: Omigov
authors.forename: A P
authors.initials: AP
authors.lastname: Agafonov
authors.forename: A N
authors.initials: AN
authors.lastname: Sergeev
mesh_terms: D000281:Administration, Intranasal; D000475:Alkenes / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology / Q000821:virology; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology*; D054833:Isoindoles / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000821:virology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000473:pathology / Q000821:virology; D051379:Mice; D008813:Mice, Inbred ICR; D012899:Smallpox / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D012901:Variola virus / Q000187:drug effects* / Q000502:physiology; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D010797:Phthalimides
chemical_list: D000475:Alkenes; D000998:Antiviral Agents; D001549:Benzamides; D006834:Hydrazines; D054833:Isoindoles; C000600130:NIOC-14; C505045:tecovirimat; D010797:Phthalimides