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Camphor based heterocyclic systems containing 1,3-thiazolidin-4-one and thiazole rings showed promising antiviral activity towards Orthopoxviruses.

A series of the bornyl ester/amide derivatives with N-containing heterocycles were designed and synthesized as vaccinia virus (VV) inhibitors. Bioassay results showed that among the designed compounds, derivatives 6, 13, 14, 34, 36 and 37 showed the best inhibitory activity against VV with the IC values of 12.9, 17.9, 3.4, 2.5, 12.5 and 7.5 μm, respectively, and good cytotoxicity. The primary structure-activity relationship (SAR) study suggested that the combination of a saturated N-heterocycle, such as morpholine or 4-methylpiperidine, and a 1,7,7-trimethylbicyclo[2.2.1]heptane scaffold was favorable for antiviral activity.

Summary 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 10 000 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 18 h post‐infection (p.i.). The highest virus titres were observed 54 h 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.

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 first example of adamantane derivatives containing monoterpene moieties that showed inhibitory activity against several orthopoxviruses.

Although the World Health Organisation had announced that smallpox was eradicated over 40 years ago, the disease and other related pathogenic poxviruses such as monkeypox remain potential bioterrorist weapons and could also re-emerge as natural infections. We have previously reported (+)-camphor and (−)-borneol derivatives with an antiviral activity against the vaccinia virus. This virus is similar to the variola virus (VARV), the causative agent of smallpox, but can be studied at BSL-2 facilities. In the present study, we evaluated the antiviral activity of the most potent compounds against VARV, cowpox virus, and ectromelia virus (ECTV). Among the compounds tested, 4-bromo-Nʹ-((1R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2ylidene)benzohydrazide 18 is the most effective compound against various orthopoxviruses, including VARV, with an EC 50 value of 13.9 μM and a selectivity index of 206. Also, (+)-camphor thiosemicarbazone 9 was found to be active against VARV and ECTV.