EVALUATION OF THERAPEUTIC-PROPHYLACTIC EFFECTIVENESS OF CHEMICAL COMPOUND NIOC-14 AGAINST ECTROMELIA VIRUS IN VIVO

Abstract

Aim. Study pharmacodynamic parameters of anti-viral effectiveness of a chemical compound NIOC-14 in experiments in mice infected with ectromelia virus (EV). Materials and methods. EV (K-1 strain) was obtained from the State Collection ofViral Infections and Rickettsioses Causative Agents of the State Scientific Centre of Virology and Biotechnology «Vector». Outbred ICR mice were intranasally infected with EV at a dose of10 LD50 per animal (10x50% lethal doses / animal) and per orally received NIOC-14 or ST-246 as a positive control. Chemical compound NIOC-14 (7-[N'-(4-trifluoromethylbenzoyl)-hidrazincarbonyl]-tricyclo[3.2.2.024]non-8-en-6-carbonic acid) was synthesized in Novosibirsk Institute of Organic Chemistry (NIOC). Anti-pox preparation ST-246, developed by SIGA Technologies Inc. (USA), was synthesized in NIOC using the technique described by the authors. Results. 50% effective doses against EV in vivo were shown not to differ significantly between the preparations NIOC-14 (3.59 pg/g mouse mass) and ST-246 (5.08 pg/g mouse mass). During determination oftherapeutic window, administration ofNIOC-14 to mice 1 day or 1 hour before EV infection, as well as 1, 2 and 4 days after EV infection and then for 9 days was found to ensure 100% animal survival. Administration of NIOC-14 as well as ST-246 resulted in the decrease relative to control ofEV titers in lungs, nasal cavity, brains, liver, spleen, kidneys and pancreas. Conclusion. Anti-viral effectiveness of NIOC-14 against EV in vivo was thus comparable by all the studied pharmacodynamic parameters with anti-viral activity of anti-poxvirus preparation ST-246.

Keywords

• mice
• orthopoxviruses
• ectromelia virus
• anti-viral activity
• anti-poxvirus chemical compound