To date, the ‘one bug-one drug’ approach to antiviral drug development cannot effectively respond to the constant threat posed by an increasing diversity of viruses causing outbreaks of viral infections that turn out to be pathogenic for humans. Evidently, there is an urgent need for new strategies to develop efficient antiviral agents with broad-spectrum activities. In this paper, we identified camphene derivatives that showed broad antiviral activities in vitro against a panel of enveloped pathogenic viruses, including influenza virus A/PR/8/34 (H1N1), Ebola virus (EBOV), and the Hantaan virus. The lead-compound 2a, with pyrrolidine cycle in its structure, displayed antiviral activity against influenza virus (IC₅₀ = 45.3 µM), Ebola pseudotype viruses (IC₅₀ = 0.12 µM), and authentic EBOV (IC₅₀ = 18.3 µM), as well as against pseudoviruses with Hantaan virus Gn-Gc glycoprotein (IC₅₀ = 9.1 µM). The results of antiviral activity studies using pseudotype viruses and molecular modeling suggest that surface proteins of the viruses required for the fusion process between viral and cellular membranes are the likely target of compound 2a. The key structural fragments responsible for efficient binding are the bicyclic natural framework and the nitrogen atom. These data encourage us to conduct further investigations using bicyclic monoterpenoids as a scaffold for the rational design of membrane-fusion targeting inhibitors.

The aim of this work was to develop and validate a sensitive and robust method of liquid chromatography coupled with tandem mass spectrometry to quantitate ST-246 (tecovirimat) in plasma using an internal standard (2-hydroxy-N-{3,5-dioxo-4-azatetracyclo [5.3.2.02.6.08.10]dodec-11-en-4-yl}-5-methylbenzamide). The method was validated in negative multiple reaction monitoring mode following recommendations of the European Medicines Agency for the validation of bioanalytical methods. The calibration curve for the analyte was linear in the 10–2500 ng/mL range with determination coefficient R² > 0.99. Intra- and inter-day accuracy and precision for three concentrations of quality control were <15%. Testing of long-term stability of ST-246 (tecovirimat) in plasma showed no degradation at −20 °C for at least 3 months. The method was applied to a clinical assay of a new antipoxvirus compound, NIOCH-14. Thus, the proposed method is suitable for therapeutic drug monitoring of ST-246 (tecovirimat) itself and of NIOCH-14 as its metabolic precursor.

This study presents results of the study of infectivity of avian influenza virus (AIV) A subtype H5N1 strains isolated from agricultural birds across the territory of the Russian Federation and CIS countries. The results of the susceptibility of chickens to the AIV isolates delivered by the aerosol route and the dissemination of the virus in the organs of infected birds are presented. As was observed, the sensitivity of birds to AIV by the aerosol route of infection is 30 times higher than by intranasal route, 500 times higher than by the oral route and 10000 times higher than by the intragastric route of infection, which is indicative of higher permissivity of respiratory organs to AIV. The highest titres of AIV A subtype H5N1(A/Chicken/Kurgan/05/2005 strain) in aerosol-infected chickens were found in nasal cavity mucosa, lungs, cloaca, serum and kidney, where viable virus accumulation was detected by 18h post-infection (p.i.). The highest virus titres were observed 54h p.i. in lungs, serum and kidney, reaching the value of 8.16 lg EID50 /g(ml) in the lungs. The results showed that birds infected by the aerosol route developed higher titres of virus than those infected by other routes.

Background: Since most of the modern human population has no anti-smallpox immunity, it is extremely important to develop and implement effective drugs for the treatment of smallpox and other orthopoxvirus infections. The objective of this study is to determine the main characteristics of the chemical substance NIOCH-14 and its safety and bioavailability in the body of laboratory animals. Methods: The safety of NIOCH-14 upon single- or multiple-dose intragastric administration was assessed according to its effect on the main hematological and pathomorphological parameters of laboratory mice and rats. In order to evaluate the pharmacokinetic parameters of NIOCH-14 administered orally, a concentration of ST-246, the active metabolite of NIOCH-14, in mouse blood and organs was determined by tandem mass spectrometry and liquid chromatography. Results: The intragastric administration of NIOCH-14 at a dose of 5 g/kg body weight caused neither death nor signs of intoxication in mice. The intragastric administration of NIOCH-14 to mice and rats at doses of 50 and 150 µg/g body weight either as a single dose or once daily during 30 days did not cause animal death or critical changes in hematological parameters and the microstructure of internal organs. The tissue availability of NIOCH-14 administered orally to the mice at a dose of 50 µg/g body weight, which was calculated according to concentrations of its active metabolite ST-246 for the lungs, liver, kidney, brain, and spleen, was 100, 69.6, 63.3, 26.8 and 20.3%, respectively. The absolute bioavailability of the NIOCH-14 administered orally to mice at a dose of 50 µg/g body weight was 22.8%. Conclusion: Along with the previously determined efficacy against orthopoxviruses, including the smallpox virus, the substance NIOCH-14 was shown to be safe and bioavailable in laboratory animal experiments.

A set of heterocyclic products was synthesized from natural (+)-camphor and semi-synthetic (−)-camphor. Then, 2-Imino-4-thiazolidinones and 2,3-dihydrothiazoles were obtained using a three-step procedure. For the synthesized compounds, their antiviral activity against the vaccinia virus and Marburg virus was studied. New promising agents active against both viruses were found among the tested compounds.

This research investigates a promising antiviral compound based on polyprenols from Siberian silver fir (Abies sibirica). The physico-chemical characteristics of a preparation developed in aerosol form and an estimation of its protective efficacy against aerosol challenge of laboratory animals are presented. It is shown that (1) by using a simple ultrasonic disperser one can obtain aerosol of three formulations studied with about 70% of its mass accumulated in the size range below 1.8 µm; (2) 40–100% of aerosol particles contain preparation for different formulations; (3) after delivering under specified schedules, the preparations as developed can protect up to 100% of mice against 5 LD₅₀ of influenza A/Aichi/2/68 (H3N2) virus aerosol infection. Animals inhaled twice the preparation doses (which were 100 times lower than injection ones of the same efficacy) and did not exceed 10 µg/mouse. It was shown that the mode of action of this immunomodulating preparation was nonspecific stimulation of immune cells' various activities.